SITC 2020 Scientific Highlights – Nov. 14, 2020

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 14, 2020, sessions of the 35th Anniversary Annual Meeting.

Method for personalized immunotherapy response prediction developed

Plasma-based proteomic profiling as a tool for predicting response to immunotherapy in melanoma patients

Michal Harel, PhD (Oncohost LTD), discussed a method for profiling patients with melanoma to predict response to immunotherapy. The group utilized proteomic profiling of plasma samples before treatment and early after initiation of anti-PD-(L)1 therapy to develop a predictive signature using machine learning. They also aimed to identify biological pathways that differed between responders and non-responders.

A 3-protein signature was developed and was able to distinguish responders from non-responders in the validation cohort with a sensitivity and specificity of 0.75 and 0.9, respectively. Using the signature, a personalized response prediction could be developed for individual patients. Further evaluation of biological pathways identified potential resistance mechanisms in non-responders, such as upregulation of inflammation, proliferation, metastasis and angiogenesis processes. Different pathways were upregulated in tumors that failed to respond to PD-(L)1 monotherapy compared to those also treated with anti-CTLA-4, indicating varying biological underpinnings for resistance. In a case study, the group discussed identification of a potential resistance-associated protein in a patient with melanoma, leading to recommendations for potential clinical trials targeting that resistance mechanism.

CD47 blockade may boost immune response to TNBC

An immune-competent tumor organoid platform to test novel immune checkpoint combinations targeting the receptor CD47 in triple negative breast cancer

Elizabeth Stirling, MS (Wake Forest School of Medicine), presented preclinical methods to investigate CD47-targeted therapies in triple negative breast cancer. The group utilized organoid tissue culture, murine models, and tissue analysis in their study. 

CD47 expression varied between primary and metastatic human TNBC tumors and was also higher in non-responding tumors than responders to PD-1 therapy. Given this, the group investigated CD47 blockade in murine models of TNBC and found that this therapy significantly decreased tumor growth. There was evidence for increased intratumoral CD8+ T cells and granzyme B expression in the tumor tissue after treatment. Treated tumors were also more sensitive to PD-L1 blockade. A 3D organoid model, which included co-incubation of tumor-specific cytotoxic T cells, was used to test CD47 therapy as well, and also revealed increased granzyme B and interferon gamma expression with treatment. The authors feel that the organoid model used in this study could be a valuable resource for future therapeutic studies.

p53-specific T cell therapy may be efficacious and widely-applicable

Adoptive T cell therapy targeting somatic p53 mutations

A p53-targeted adoptive T cell therapy was discussed by Peter Kim, PhD (National Cancer Institute). Given that p53 is the most commonly-mutated cancer driver gene, cell therapies targeting common p53 mutations may be widely-applicable.

The group found that 22% of screened patient TILs were responsive to mutant p53, which included 46 different TCRs. However, patients that were treated with autologous TILs largely did not respond to the therapy, with 2 PRs found in 12 patients. The infused TILs were found to have low frequencies of mutant p53-specific TILs, and had a high level of differentiation and exhaustion. The group hypothesized that genetic engineering of T cells may overcome these problems and thus treated a patient with breast cancer with adoptive transfer of autologous PBLs that had been retrovirally transduced with an anti-p53 R175H TCR. The patient’s tumors shrunk by 55% after this treatment, despite having progressed on 10 other therapies. The engineered cells were found to be more persistent and have greater p53 reactivity than naturally-occurring TIL, making this strategy a promising one for future wide-scale immunotherapy.

SITC 2020 Scientific Highlights – Nov. 13, 2020

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 13, 2020, sessions of the 35th Anniversary Annual Meeting.

Combination ICI shows benefit for angiosarcoma

A multicenter phase II trial (SWOG S1609, Cohort 51) of Ipilimumab and Nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

Michael Wagner, MD (University of Washington), presented the results from cohort 51 of the SWOG S1609 DART trial, which investigated combination nivolumab and ipilimumab in patients with angiosarcoma. Sixteen patients were enrolled in this cohort with the primary endpoint of response rate.

The overall response rate was 25%, which included partial responses in three patients with cutaneous disease of the scalp/face and one patient with radiation-associated breast angiosarcoma. Six-month progression free survival was estimated at 38% across all patients. Molecular tumor characterization was performed in eight patients and revealed at least two deleterious genomic alterations in each patient, though these were unique to each individual. Responders in this cohort tended to have intermediate to high tumor TMB, though data was only available for two responders. Adverse event profiles were as expected. Given the encouraging results in this aggressive cancer, future study is anticipated.

Triplet therapy may benefit pancreatic cancer

Urelumab (anti-CD137 agonist) in combination with vaccine and nivolumab treatments is safe and associated with pathologic response as neoadjuvant and adjuvant therapy for resectable pancreatic cancer

Lei Zheng, MD, PhD (Johns Hopkins University School of Medicine), and colleagues investigated the treatment of pancreatic cancer with combination urelumab, nivolumab and a vaccine, GVAX. Preclinical and early clinical studies by the investigators indicated that adding the anti-CD137 antibody urelumab to the other two therapies could be synergistic, initiating this study. Ten patients without previous treatment were enrolled.

Patients received one dose of each therapy, followed by R0 resection two weeks later. Following surgery, patients were treated with additional immunotherapy cycles in addition to standard-of-care chemotherapy. No patients had to delay surgery due to toxicities, and three patients exhibited moderate pathologic responses at the time of surgery, which was not anticipated. Nine of the ten patients remain disease-free at a median follow-up of one year. No notable safety signals were seen, with the most common toxicity being nausea. A trend toward an increase in activated T cells (evidenced by granzyme B expression) was noted after the combination treatment, along with expansion of T cell clones expressing granzyme B and PD-1.

Antibody targeting p53 peptide complex shows therapeutic promise

Targeting a shared TP53 neoantigen with bispecific T cell retargeting antibody

Emily Hsiue, MD (Johns Hopkins University School of Medicine), discussed a T cell retargeting antibody, known as H2, which recognizes CD3 on T cells and a mutant peptide presented by HLA resulting from p53 mutations. As TP53 is the most commonly-mutated cancer driver gene, the group anticipated that a therapy targeting a shared neoantigen resulting from these mutations would be widely-applicable.

Using a phage display library, an scFv was identified that specifically binds p53 R175H/HLA-A*02:01. Linking this neoantigen-specific scFV with an anti-CD3 scFv generated the H2 MANAbody (mutation-associated neoantigen), which was tested in vitro and in vivo. Cellular studies verified that the agent was able to induce cytotoxicity against cancer cells expressing the mutant peptide but not the wild-type, including cells that were engineered to express the antigen and those at endogenous levels. Murine studies using xenograft tumors also demonstrated therapeutic efficacy. The authors hypothesize that their approach of targeting HLA-bound peptides may increase the pool of potentially actionable therapeutic targets.

Radiotherapy, anti-CTLA-4 and CD40 agonism may synergize

Radiotherapy and CTLA-4 blockade expand anti-tumor T cells differentiation states and cooperate with CD40 agonist to induce tumor rejection

The mechanisms behind the combination of radiotherapy and anti-CTLA-4 treatment were investigated by Nils Rudqvist, PhD (Weill Cornell Medicine/MD Anderson Cancer Center), and colleagues. The group employed the murine 4T1 model to dissect the T cell response to these therapies and other combinations in order to determine potential synergistic therapies.

The combination of radiotherapy and anti-CTLA-4 therapy induced clonal expansion and tumor infiltration of T cells in these preclinical models, increasing both these measures over either therapy alone. Each individual therapy impacted different T cell compartments. Radiotherapy boosted effector T cell populations, increasing CD8+Gzmb+Lag3+Pd1+ cells, while CTLA-4 monotherapy boosted Th1 cells, expressing CD4, CD40lg and IFNg. The combination had the most impact on CD8+TNF+Ifng+ polyfunctional cells. The group tested additional therapeutic combinations based on these T cell population results, including the addition of antibodies targeting PD-1, LAG-3, and CD40. The addition of a CD40 agonistic antibody to the radiotherapy and CTLA-4 combination resulted in increased therapeutic efficacy and better tumor control, while the other two additions had no effect. This triplet combination may represent a future avenue for improving immunotherapy effectiveness in patients.

B cell vaccination may boost immune response to glioblastoma

B-cell-based vaccination elicit potent immunity against glioblastoma

A B-cell-based vaccination therapy for glioblastoma was discussed by Catalina Lee-Chang, PhD (Northwestern University). This therapy, known as Bvax, was developed by activating 4-1BBL+ B cells in vitro using CD40 and IFNgamma receptor ligation, in addition to incubation with tumor cell lysate. These activated B cells could then be intravenously administered to mice bearing glioblastoma tumors or tested in vitro for their effects on tumor cells.

In vitro studies indicated improved tumor cell killing by T cells with co-incubation of Bvax in a concentration-dependent manner. Enhanced CD8+ T cell activation and infiltration into the tumor-bearing brain was observed after co-administration of Bvax and tumor-specific T cells in mouse models. Bvax also primarily produced IgG antibodies in vivo, which were tumor-reactive. Administration of these Bvax-derived IgG to tumor-bearing mice was able to extend their survival. A combination therapy of radiotherapy, Bvax, CD8+ T cells, and anti-PD-L1 was able to significantly extend the survival of tumor-bearing mice as well, also increasing T cell infiltration in the brain. The role of B cells is thus important to explore in order to improve the responsiveness of “cold” tumors to immunotherapy.

Combination PI3K-g and PD-1 inhibition benefits ICI-experienced patients with SCCHN

Updated clinical data from the squamous cell carcinoma of the head and neck (SCCHN) expansion cohort of an ongoing Ph1/1b Study of eganelisib (formerly IPI-549) in combination with nivolumab

Ezra Cohen, MD (University of California, San Diego), presented findings from the phase 1/1b study, MARIO-1, investigating the combination of eganelisib and nivolumab in patients with squamous cell carcinoma of the head and neck that progressed on prior PD-(L)1 therapy. Patients received eganelisib, a PI3K-g inhibitor, at 40 mg QD PO and nivolumab 240 mg Q2W. Twenty-one patients with head and neck cancer were included in this analysis.

The safety profile of the combination was largely as expected, with the most common treatment-related adverse events including fatigue, nausea, pyrexia and pruritis. The overall response rate in patients with tumors that had progressed on immediate prior PD-(L)1 therapy (n=20) was 10%, with both of the partial responses occurring in patients with 1-2 prior lines of therapy. For patients with 3+ prior therapies, no responses were noted, though 5/10 patients did experience stable disease. Median PFS in the whole population was 17 weeks. Higher benefit was noted in patients with HPV+ tumors, as 50% of these achieved stable disease, while none of the HPV- tumors did. The investigators are beginning a window-of-opportunity study in HNSCC based on the findings in this trial.

SITC 2020 Scientific Highlights – Nov. 12, 2020

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 12, 2020, sessions of the 35th Anniversary Annual Meeting.

Investigations of oncolytic viruses in glioblastoma reveal immunological differences

Comparison of Two oHSV Vectors for the Treatment of Glioblastoma

Joseph Jackson, PhD (University of Pittsburgh), and colleagues compared two oncolytic herpes simplex virus vectors for their efficacy in treating preclinical glioblastoma. The two strains included an HSV-1 KOS strain called KG4:T124 and an F strain derivative called rQNestin34.5v.1, and were tested in the murine syngeneic GL261N4 and CT2A models and in vitro assays.

In vitro tests revealed that both viruses entered cells with similar efficiency, but that rQNestin34.5v.1 was able to induce greater viral-mediated cytotoxicity due to a higher replication rate. Analysis in the GL261N4 model showed that rQNestin34.5v.1 also increased animal survival through reduced tumor burden, but increased efficacy was not noted with repeated injections of this virus. However, multiple injections of KG4:T124 did improve the efficacy of this virus in the GL261N4 orthotopic model through increased survival. Neither virus was able to control the more aggressive CT2A tumors. Increased tumor infiltration of tumor-associated macrophages and polymorphonuclear cells was seen after treatment with each virus, but an increase in beneficial anti-tumor immune cells, like NK or T cells, was not noted. Ongoing preclinical investigations like this one may help to elucidate the mechanisms of response and resistance to immunotherapies in difficult-to-treat glioblastoma.

Immune checkpoint inhibition may be effective for certain leptomeningeal metastases

Pembrolizumab for Patients with Leptomeningeal Metastasis from Solid Tumors: Efficacy, Safety and Cerebrospinal Fluid Biomarkers

An investigation of pembrolizumab for the treatment of leptomeningeal metastases was presented by Jarushka Naidoo, MB, BCH, MHS (Johns Hopkins Sidney Kimmel Cancer Center). Thirteen patients with leptomeningeal metastases from solid tumors, including HR+ breast cancer, glioma, NSCLC, head and neck carcinoma, and cutaneous squamous cell carcinoma, were treated on the trial and followed for the primary endpoint of CNS response after 4 cycles.

A CNS response was recorded in 38% of patients on the trial, which included durable complete responses in a patient with cutaneous squamous cell carcinoma (OS: 3+ years) and another with MET-exon14+ NSCLC (OS: 9 months). One patient experienced a partial response and two patients displayed stable disease in the CNS. Overall, the median PFS in the CNS was 2.9 months and the median OS was 4.9 months. A cytokine analysis indicated that there were differences between responders and non-responders, such as reduction in levels of certain pro-inflammatory cytokines in responders. The investigators also determined that detection of tumor DNA in the CSF may be a better method for detecting leptomeningeal metastases than the currently-used technique of CSF cytology. This study indicates that immune checkpoint inhibition may be a tool for managing leptomeningeal metastases from certain cancers.

Extracellular vesicle PD-L1 may predict response to ICIs in NSCLC

Dynamic change of PD-L1 expression on extracellular vesicles predicts response to immune-checkpoint inhibitors in non-small cell lung cancer patients

Diego de Miguel Perez, PhD, MSc (University of Maryland), discussed a study of extracellular vesicles as biomarkers in patients with NSCLC. Patients in the trial were receiving immune checkpoint inhibitors for advanced/metastatic NSCLC and had tissue samples collected at baseline and plasma samples (to evaluate extracellular vesicles) collected at baseline and at first response evaluation eight weeks later.

Contrary to some other studies, tissue PD-L1 expression did not correlate with treatment response in this cohort, nor was it correlated with baseline PD-L1 levels on extracellular vesicles (EVs). A trend was observed in the dynamics of PD-L1 expression on extracellular vesicles, however, as patients who did not respond to checkpoint inhibition tended to have PD-L1 levels increase on EVs throughout treatment. Similarly, patients with a response to therapy showed stable or decreasing levels of PD-L1 on EVs, as measured by immunoblot. The increase in PD-L1 on EVs was thus significantly associated with shorter overall survival (HR: 4.34, p=0.037) and shorter progression-free survival (HR: 5.06, p=0.025). EVs should be evaluated in larger cohorts of patients to validate their use as a non-invasive biomarker.

Novel agent may control ICI colitis without impacting cancer treatment efficacy

Preclinical development of a novel colon-targeted therapeutic for the treatment of Immune Checkpoint Inhibitor (ICI)-colitis

Nazli Dizman, MD (Yale New Haven Hospital), presented a preclinical investigation of a novel colon-targeted immunosuppressive agent for the management of immunotherapy-induced colitis. The agent, VV2003, is a selective CRAC inhibitor that is administered orally and has low epithelial permeability in the gut to limit systemic absorption and effects, like inhibiting responses to immunotherapy.

Pharmacokinetic studies in mice verified low plasma exposure of VV2003 and high levels in the colon regardless of inflammation status. The agent was also tested in murine models of colitis, showing improvements in colitis markers like histology scores, colon myeloperoxidase, and endoscopy scores over treatment with a vehicle. Importantly, treatment of mice with VV2003 did not appear to impact the efficacy of immune checkpoint inhibition on tumor growth. An ongoing study is investigating the impact of VV2003 on colon samples from patients with suspected immune-related colitis. With two patients to date, there appears to be a reduction in MCP-1 after treatment, though future studies are needed to confirm the influence of VV2003 in human patients, including a planned phase 1a/b trial.

DLL3 bispecific T cell engager may be effective for SCLC management

AMG 757, a half-life extended bispecific T-cell engager (BiTE®) immune therapy against DLL3 in SCLC: phase 1 interim results

A phase 1 trial of AMG 757, a T cell engager against DLL3, in small cell lung cancer was discussed by Hossein Borghaei, DO, MS (Fox Chase Cancer Center). The agent combines anti-CD3 and anti-DLL3 domains with an Fc region to increase circulation half-life. This study, as the first-in-human investigation, followed a dose exploration/expansion format with target doses from 0.003 to 10 mg. Forty patients were enrolled, all of whom had received at least one prior systemic therapy for SCLC.

Treatment-related adverse events of any grade were noted in 80% of patients, with 18% being grade 3+. The most common any-grade event was cytokine release syndrome, though these were all of grade 1-2 and most common with the first dose of AMG 757. There was one instance of grade 5 pneumonitis. Across all dose levels, confirmed partial responses were noted in 16% of patients, all at doses of at least 0.3 mg. the four-week disease control rate in the study was 45%. Responses are ongoing in 5/6 patients with a median follow up of 8.8 months. Investigation of this agent, including determining the optimal monotherapy dose, is still ongoing.

SITC 2020 Scientific Highlights – Nov. 11, 2020

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 11, 2020, sessions of the 35th Anniversary Annual Meeting.

AXL and PD-1 inhibition may benefit select patients with non-small cell lung cancer

A PhII study of bemcentinib, a first-in-class selective AXL kinase inhibitor, in combination with pembrolizumab in pts with previously-treated advanced NSCLC: Updated clinical & translational analysis

James Spicer, PhD FRCP (King’s College London), discussed the BGBC008 trial, investigating the combination of the AXL inhibitor bemcentinib with pembrolizumab for non-small cell lung cancer. Results were presented for the cohort of patients who had progressed on prior immunotherapy with the primary endpoint of overall response rate.

Sixteen patients were included in this analysis, all of whom had been treated with an immune checkpoint inhibitor as their most recent therapy. Biomarker status was available for 13 patients: 8 were cAXL-positive while 5 were negative, and 5 patients had PD-L1 TPS >=50%, 5 had TPS of 1-49%, and 3 had TPS <1%. Responses to the combination therapy were only observed in patients with cAXL positivity (combined tumor and immune cell expression), as 1 partial response and 5 stable disease results were recorded in these seven patients. Median PFS for AXL-positive patients was 4.73 months compared to 1.87 months for cAXL-negative. Common treatment-emergent adverse events included liver enzyme elevations and diarrhea. The authors proposed that AXL may promote T cell dysfunction and exhaustion, among other mechanisms, and blocking this function could potentiate immune checkpoint blockade therapy, even in these patients who progressed on prior immunotherapy.

Combination of bempegaldesleukin and nivolumab results in long PFS in melanoma

Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study

Updated results from the PIVOT-02 study, investigating the combination of nivolumab and the IL-2 pathway agonist bempegaldesleukin, were presented by Adi Diab, MD (MD Anderson Cancer Center). Patients (n=41) were eligible for the trial if they had previously untreated metastatic melanoma and were evaluated for the primary endpoints of overall response rate and safety.

The median follow-up for this report was 29.0 months. At this time, the ORR was 53%, including a complete response rate of 34%. The median time to response was 2.0 months, and to complete response was 7.9 months. The median PFS was 30.9 months, and the median overall survival was not reached. The 36-month OS rate was 70.9%. Biomarker studies revealed signatures that correlated with response, including the interferon-gamma gene expression profile and CD8+ TILs in baseline samples. Dynamic changes in the peripheral blood were also observed after the first dose of treatment, resulting in increases in the polyfunctional strength index of CD4+ and CD8+ T cells, and in the level of circulating eosinophils. The encouraging findings in this phase 2 trial have led to the initiation of a phase 3 trial of the same combination.

Neoadjuvant oncolytic virus therapy may benefit patients with melanoma

3-year results of the phase 2 randomized trial for talimogene laherparepvec (T-VEC) neoadjuvant treatment plus surgery vs surgery in patients with resectable stage IIIB-IVM1a melanoma

Reinhard Drummer, MD (University Hospital of Zurich), and colleagues studied the use of talimogene laherparepvec (T-VEC) as a neoadjuvant treatment for patients with resectable melanoma in a phase 2 trial. This presentation provided an interim analysis of the impact of neoadjuvant T-VEC compared to surgery alone with a median follow up of 41.3 months.

The primary analysis of recurrence-free survival indicated improved outcomes with neoadjuvant T-VEC, as these patients experienced 3-year RFS rates of 46.5% compared to 31.0% with surgery alone by Kaplan-Meier estimates. Removing potential effects of subsequent therapies increased the difference between the two arms, with estimated 3-year RFS of 49.1% with T-VEC and 22.9% without. Overall survival was also greatly improved with neoadjuvant therapy: 3-year estimates were 83.2% compared to 71.6%. This first trial of neoadjuvant oncolytic virus therapy is therefore showing encouraging results and warrants continued evaluation.

Study compares neoadjuvant options for non-small cell lung cancer

Combined neoadjuvant chemo-immunotherapy therapy achieves superior downstaging of resectable non-small cell lung cancer as compared to chemotherapy, mono or dual immunotherapy

As neoadjuvant approaches with immunotherapies are gaining attention, Boris Sepesi, MD (MD Anderson Cancer Center), and colleagues compared outcomes with four treatment options: platinum doublet chemotherapy, nivolumab, nivolumab + ipilimumab, or nivolumab + doublet chemotherapy. The patient cohorts were pulled from institutional records and the NEOSTAR study, and were diagnosed with stage I-IIIA NSCLC.

The highest rate of overall clinical-to-pathological downstaging (ypT and/or ypN) was found in the cohort of patients treated with nivolumab and chemotherapy at 68%, while all three other treatment options led to overall downstaging rates of 38% (p=0.048). Upstaging rates also favored patients receiving nivolumab and chemotherapy, as only 14% of these patients were upstaged at the time of surgery, compared to 28% of the chemotherapy cohort and 38% of patients in both the nivolumab and nivolumab + ipilimumab cohorts. The only evaluation that did not favor the nivolumab + chemotherapy treatment was the ypN downstaging, where the lowest rate of downstaging (42%) was seen with this treatment and the highest rate (55%) with chemotherapy. While these downstaging rates are encouraging, it remains to be seen whether these rates in small cohorts extend to improved survival.

Combination nivolumab and intratumoral therapy may be promising neoadjuvant option for melanoma

Phase II Trial of Neoadjuvant Nivolumab (Nivo) and Intra-Tumoral (IT) CMP-001 in High-Risk Resectable Melanoma (Neo-C-Nivo): Final Results

Diwakar Davar, MD (UPMC Hillman Cancer Center), discussed a trial of combination nivolumab and intratumoral CMP-001 (a CpG packaged in a virus-like particle) in patients with high-risk resectable melanoma. Thirty patients were treated with a combination of neoadjuvant and adjuvant therapy. The neoadjuvant portion included seven weeks of weekly CMP-001 delivered intratumorally after the first week and three doses of nivolumab. After resection, nivolumab and CMP-001 were dosed every four weeks for 48 weeks. Primary goals of the study were to evaluate major pathological response rate and safety.

All but one patient completed the full neoadjuvant therapy cycle, with two patients discontinuing CMP-001 due to toxicity. Radiographic analysis indicated response in 43% of patients and stable disease in 30%. Pathologic responses included complete response in 50%, major pathologic response in 10%, and partial response in 10%. Biomarker analysis indicated that responding tumors had increased levels of CD8+ TIL and CD303+ plasmacytoid dendritic cells. The median relapse-free survival has not been reached in patients with pathological responses, leading the investigators to continue further investigation of this combination.

President's Message - August 2020

Dear Colleagues,

By this time, you are probably already aware that we will hold our society’s 35^th Annual Meeting & Pre-Conference Programs (SITC 2020) as a fully virtual event. We’ve made several recent announcements involving SITC 2020, including:

• Online registration is now open, please register today
• SITC members can attend the entire SITC 2020 for free – join SITC or renew your membership today
• The dates for SITC 2020 are finalized, beginning and ending a day earlier, now Nov. 9–14, 2020
• Deadlines to submit abstracts to SITC 2020 have been extended to Aug. 25, 2020, by 5 p.m. PDT – click here to learn more about SITC 2020 abstract information

Our preference was to find a way to safely convene in person. However, the coronavirus pandemic is still active, the course of the pandemic over the next several months is difficult to predict, and the safety of our members, their families, and our patients is our highest priority. Therefore, the decision to go virtual became necessary. We understand that a virtual event removes the prospect of the invaluable, sometimes spontaneous in-person conversations that can lead to important insights, collaborations, and for some members, important career opportunities.  But we hope and are working very hard to make the 2020 Virtual Annual Scientific Meeting a truly unique, highly productive and beneficial experience for all of this year’s attendees. And perhaps by going virtual we can expand the opportunity to connect to a much broader group of our members around the world.

To provide researchers with more time to prepare their SITC 2020 abstracts for our reimagined virtual meeting, we will extend the submission deadline for regular and Young Investigator Award abstracts, late-breaking abstract applications and presentation applications for the Immunotherapy Resistances and Failure program until Aug. 25, 2020, at 5 p.m. PDT. This extension provides nearly a month of additional time for colleagues to prepare their work for viewing in the virtual poster hall and potentially as a recorded presentation. Click here to view the updated abstract timeline and related important dates for SITC 2020.

As this is SITC’s 35^th Anniversary Annual Meeting, one of the many highlights will be three keynote opening addresses from highly accomplished scientists in our field. I have the privilege to introduce several of the SITC 2020 faculty, including the following keynote presenters:

Richard V. Smalley, MD Memorial Award and Lectureship:

• Gordon Freeman, PhD (Dana-Farber Cancer Institute) – “The PD-L1/PD-1 Pathway: Discovery and New Insights”
• Lieping Chen, MD, PhD (Yale School of Medicine) – “Why Were We Interested in Immunity Within the Tumor Microenvironment in the 1990s?”
• Arlene Sharpe, MD, PhD (Harvard Medical School) – “Discovery of New IO Targets and Mechanisms Leveraging CRISPR”

 Keynote Address:

• Elizabeth M. Jaffee, MD (Sidney Kimmel Cancer Center, Johns Hopkins University) – “Turning Immunologically Quiescent Tumors into Immune Responsive Cancers”

35^th Anniversary Keynote Address:

• Helen E. Heslop, MD (Baylor College of Medicine) – “T cell Therapy of Cancer”

These presentations and many more, including late-breaking research, reflect the very high scientific quality of the SITC 2020 meeting. You can access the meeting without cost if you are an SITC member,  so if you have not yet done so, join the SITC family or renew your membership for 2020 and beyond by  completing the SITC 2020 online registration.

Planning for SITC 2020 consumed much of our leadership’s recent discussions, but we continue to focus on the long-term future of the society. In mid-July, I was honored to welcome a collection of respected SITC member leaders, representing a variety of professional backgrounds and interests, to the annual SITC strategic planning retreat. The meeting was hosted on the Zoom platform to ensure the safety of all participants. This esteemed group engaged in productive discussions that outlined future society outputs for key scientific issues; considered SITC’s approach to future live and virtual educational programs in our new global environment; and addressed ways to increase our society’s commitment to racial and ethnic diversity. As always, I was impressed by the thoughtfulness of our leaders in addressing opportunities and potential problems for our Society.

An important area of SITC strategic focus is policy and advocacy, and these efforts are particularly important now to ensure continued progress of the immunotherapy community through the global pandemic. SITC-drafted text was incorporated into the Fiscal Year 2021 U.S. House of Representatives Agriculture Subcommittee Bill regarding annual financial appropriations for the U.S Food and Drug Administration. Thanks to the efforts of our SITC Policy Committees, 2020 marks the third consecutive year SITC was able to place congressional language which communicates SITC member priorities to the FDA. We invite you to learn more about SITC's policy and advocacy efforts here, and view the FY21 FDA appropriations language focused on combination immunotherapies here.

This year has been a particularly difficult year for everyone with new and unexpected challenges. I would like to thank the entire SITC family–my colleagues on the Board of Directors, Executive Committee, SITC committees and task forces, staff and many others–for your continued dedication and unflinching support of our society. It is this collective effort that will ensure our Society and our field of a bright future.

Sincerely,

Mario Sznol, MD

SITC President

President's Message - July 2020

Dear Colleagues,

As I hope many of you saw recently, SITC announced its intentions to transition the upcoming 35^th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) on Nov. 10–15, 2020, from an in-person conference to a fully virtual event. The decision, made with the full support of the SITC Executive Committee and Annual Meeting organizers, will allow our society to convene safely amid the global coronavirus pandemic while sharing and celebrating the continued progress achieved in the cancer immunotherapy field.

SITC 2020 reimagined as a fully virtual experience will ensure the health and safety of our participants and their patients while providing new, unique opportunities to connect with an expanded global audience. In celebration of our society’s 35^th anniversary, we are excited to offer free SITC 2020 registration to all SITC members. Online registration for SITC 2020 reimagined will open in the coming weeks. Join the SITC family or renew your membership today to ensure your eligibility for free SITC 2020 participation. Stay tuned for much more in the coming weeks as we announce new and exciting features of SITC 2020 reimagined as a virtual event.

While the coronavirus pandemic has greatly affected our lives, professionally and personally, it is vital we continue the mission of our great society to improve cancer patient outcomes by advancing the science, development and application of cancer immunology and immunotherapy. One of the means by which SITC strives to achieve this mission is through programs that provide funding and recognize the scientific achievements of our field’s early career scientists. The pandemic has undoubtedly impacted funding for young investigators, and thus, such continued support from SITC is more important than ever. In June, we recognized a record-breaking number of early career scientists as recipients of our society’s 2020 Postdoctoral Cancer Immunotherapy Fellowships and Award.

Thanks to the continued and generous support of our industry partners—Amgen, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, Inc. and Merck—SITC was able to award six early career scientists with fellowships, totaling $600,000 in one- and two-year awards. In a new collaboration with NanoString Technologies, SITC was also able to offer an award providing access to the company’s spatial profiling technology to further research.

I would like to congratulate this year’s recipients of the 2020 Postdoctoral Cancer Immunotherapy Fellowships and Award:

• SITC-Merck Cancer Immunotherapy Clinical Fellowship: Joseph Clara, MD – National Institutes of Health (NIH)

• SITC-AstraZeneca Immunotherapy in Lung Cancer Clinical Fellowship: Jacob Kaufman, MD, PhD – Duke University Medical Center

• SITC-Amgen Cancer Immunotherapy in Hematologic Malignancies Fellowship: Suman Paul, MBBS, PhD – Johns Hopkins School of Medicine

• SITC-Bristol Myers Squibb Postdoctoral Cancer Immunotherapy Translational Fellowship: Li Qiang, PhD – Dana-Farber Cancer Institute, Harvard Medical School

• SITC-NanoString Technologies Spatial Profiling Award: Todd Triplett, PhD – University of Texas Dell Medical School

• SITC-Genentech Women in Cancer Immunotherapy Fellowship: Natalie Vokes, MD – Dana-Farber Cancer Institute

• SITC's Holbrook Kohrt, MD, PhD Cancer Immunotherapy Translational Memorial Fellowship (Sponsored by Genentech): Kipp Weiskopf, MD, PhD – Whitehead Institute for Biomedical Research 

To learn more about these individuals and their research, please visit our website. Thank you to all of this year’s SITC Fellowships and Award applicants and sponsors! Please look for a host of new funding opportunities in January.

I would also like to congratulate the 2020 National Cancer Institute (NCI) Immunotherapy Fellowship recipient, John Shin, MD, from Mayo Clinic Rochester. Dr. Shin will be exposed to multiple clinical immunotherapeutic approaches and key opinion leaders in the field of cancer immunotherapy at NCI’s Center for Cancer Research. The NCI Immunotherapy Fellowship is co-sponsored by the NCI of the National Institutes of Health (NIH) and SITC and made possible in part by an educational grant from EMD Serono.

SITC will honor this year’s awardees, along with many other young investigators, during our awards ceremony at the 35^th Anniversary Annual Meeting. We will also recognize an additional 35 early career scientists as part of our society’s Young Investigator Awards. These accolades, which include the highly coveted Presidential Award, reward excellence in SITC Annual Meeting oral abstract and poster presentations. We are also eager to recognize the numerous basic scientists, translational researchers and clinicians working to improve cancer patient outcomes.

As a reminder, regular abstracts, Young Investigator Award abstracts, late-breaking abstracts and Immunotherapy Resistance and Failure Pre-Conference Program presentation applications are due by 5 p.m. PDT on Friday, July 31. For a complete listing of SITC 2020 abstract categories, which now includes research on COVID-19 and immunotherapy, please click here.

Finally, I would like to share proudly that the Journal for ImmunoTherapy of Cancer (JITC) increased its Impact Factor this year to 9.913. This Impact Factor makes JITC the highest ranked fully open access immunology journal and places JITC in top 8 percent of all journals published in the oncology and immunology categories. Congratulations to JITC Editor-in-Chief Pedro Romero, MD, the JITC Editorial Board, its vast collection of reviewers and staff for this honor.

Please consider submitting your research to JITC or becoming a reviewer as the journal furthers its mark as a respected source for research in oncology.

Sincerely,

Mario Sznol, MD

SITC President

President's Message - December 2019

Dear Colleagues,

I would like to begin my final President's Message of 2019 by expressing our sincere appreciation to the 4,800 cancer immunotherapy professionals who attended our society's 34th Annual Meeting & Pre-Conference Programs (SITC 2019) in National Harbor last month. The research findings presented at the meeting demonstrated the exciting progress in our field at the bench and the bedside and point us in the direction of finding improved treatments for our patients. The path to a cure for most patients remains difficult, but SITC 2019 again showed that our growing community is capable and committed to achieve this mission.

I'd like to share important highlights of the past year which were possible only because of the outstanding efforts of our members, society leadership and SITC staff. Beyond the clear success that was SITC 2019, our society hosted numerous educational and scientific programs throughout the year, including Advances in Cancer Immunotherapy™ series around North America and workshops on cancer immune responsiveness and adoptive cellular therapies. Additionally, SITC launched new and/or expanded several initiatives to expand opportunities for our members including the Women in Cancer Immunotherapy Network, Cancer Immunotherapy Winter School and the SITC Volunteer Portal. We should all feel proud of one key milestone for this year; SITC eclipsed 3,000 members for the first time in its history – an increase of more than 500 members this year.

In the past 11 months, we also developed bold and ambitious plans for SITC's immediate future. Earlier this year, executive leadership confirmed our society's 2019–21 strategic goals, to include the following:

• Education and Scientific Exchange: Serve as the leading resource for information and education on cancer immunotherapy 
• Professional Standards: Set industry standards for the field of cancer immunotherapy in order to position SITC as the authority on immunotherapy of cancer 
• Global Access and Impact: Advance the science and application of cancer immunotherapy worldwide 
• Policy and Advocacy: Inform and influence the science and research, regulation, as well as quality of care and quality of access impacted by public policy, ensuring the patient voice is heard and recognized 
• Science and Research: Challenge the thinking and seek the best research in the exploration and development of tumor immunology and cancer immunotherapy 
• Leadership Development: Cultivate the next generation of leaders and innovators in tumor immunology and cancer immunotherapy

These six strategic goals are extensions of our historic goals and provide an ambitious agenda and direction for our society's leaders in the next few years. Together, work to achieve each of the goals will bring SITC closer to its ultimate mission, which is to improve cancer patient outcomes by advancing the science, development and application of cancer immunology and immunotherapy. In January, I'll report on plans to fulfill our six strategic goals in 2020.

There is still time in the current year to make progress on one of our most important objectives, leadership development. I invite you to join me in supporting the future of our field through a donation to SITC's Forward Fund. Since 2012, the Forward Fund has awarded more than $3.2 million toward programs, grants and initiatives that support early career scientists through research and education. Please consider making an end-of-year donation to the Forward Fund by Dec. 31, 2019, and your gift will be matched by an anonymous donor.

I would like to thank everyone who contributed toward the success of SITC in 2019. I look forward to the year ahead, working with all of my colleagues, to help SITC advance science and clinical care of cancer patients. Finally, I wanted to share a quick reminder about our online event on Wednesday (tomorrow). SITC will live stream its Advances in Cancer Immunotherapy™ (ACI) program (which is also occurring in-person in Nashville, Tenn.) on Dec. 4, beginning at 4:25 p.m. EST. ACIs are CME-, CPE-, CNE- and MOC-certified programs featuring nearly five hours of engaging cancer immunotherapy education that is free for healthcare professionals in the clinical setting, students and patient advocates. Click here to learn more and register for tomorrow's webcast.

I wish you a happy and safe holiday season.

Sincerely,

Mario Sznol, MD
SITC President

SITC 2019 Scientific Highlights - Nov. 10

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 10, 2019, sessions of the 34th Annual Meeting.

Role of Sirt2 in T cell activity elucidated

Sirt2 inhibition enhances anti-tumor immunity by promoting T cell metabolism

Abstract O51

Imene Hamaidi, PhD – Moffitt Cancer Center

A possible mechanism for improving anti-tumor immune responses was proposed by Dr. Imene Hamaidi (Moffitt Cancer Center). The role of Sirt2 in immune responses is debated; therefore, this study aimed to elucidate its role in T cell metabolism and function, using murine studies and ex vivo analysis of T cell activity, metabolites, and other immune markers.

In mouse models, Sirt2 deficiency led to a hyper-reactive T cell phenotype, which endowed these mice with an increased capacity to reject engrafted tumors. Similarly, Sirt2-/- T cells exhibited improved anti-cancer activity and hypermetabolism. Upon T cell activation, Sirt2 was observed to interact directly with PFKP, GAPDH, enolase, and aldolase glycolytic pathway enzymes, and modified their activity. Through analysis of tissue samples from clinical trials, patients with increased Sirt2 expression in their TILs were found to have poorer responses to immunotherapy, providing more support to the preclinical studies. Inhibition of Sirt2 pharmacologically increased the effector capacity of human T cells in culture as well. Therefore, the Sirt2 pathway warrants further investigation to improve outcomes to immunotherapy treatments.

Genetic markers for TIL responsiveness identified

The road-map to tumor-infiltrating lymphocyte (TIL) therapy: Understanding genetic alterations for improved patient treatment

Abstract O5

Caitlin Creasy, MS – MD Anderson Cancer Center

Biomarkers for response to TIL therapy in melanoma were presented by Caitlin Creasy, MS (MD Anderson Cancer Center). Pre-treatment tumor tissue samples were analyzed using whole exome (WES) and RNA sequencing and immunohistochemistry to generate correlations with treatment response, progression-free survival, and overall survival.

Overall survival, but not PFS or response, could be predicted from WES results, with a higher neoantigen burden indicative of longer survival. Two genetic mutations were enriched in the overall patient cohort – KCNQ2 and SFTA3. These mutations occurred at a rate higher than that observed in TCGA (1.9 vs 13% and 0.6 vs 6%, respectively), which the authors hypothesized to be a result of the higher-stage cohort in this study relative to the TCGA population. Samples from recurring tumors did not indicate any driver mutations, but changes in the abundance of tumor subclones were observed. From RNAseq, three genes were found to correlate with better outcomes: PDE1C, RTKN, and NGFR; at the same time, ELFN1 was enriched in patients with worse outcomes. Recurrent tumors were found to have markers of a mesenchymal phenotype as well. This study therefore presents possible biomarkers for response, as well as possible pathways of immune escape.