The Sentinel

THE OFFICIAL BLOG OF THE SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC).

Thursday, January 16, 2020

JITC Letter from the Editor - January 2020


pedro-romero_1__1_.jpgDear JITC Readers,

Welcome to the first JITC Digest of 2020! The past decade has seen cancer immunotherapy advance to an incredible degree, and the pace of innovation is not looking to slow down any time soon. It is an exciting time for the field and for the journal as JITC continues to expand and evolve to serve the community.

To support our continued growth, JITC has partnered with a new publisher, BMJ, which will allow the journal to offer an improved experience for authors, editors, reviewers and readers at all steps during the publication process. You can read more about the transition in a special editorial in the January issue.

Additionally, JITC will now offer two new sections focusing on exciting emerging areas in our field: Immune Cell Therapy and Immune Cell Engineering, edited by Dr. Marcela V Maus, and Oncolytic Immunotherapy, edited by Dr. Howard L Kaufman. We’re thrilled to help usher these important and innovative approaches into more widespread clinical use.

The highlighted papers in this month’s digest truly exemplify the tremendous pace of advancement within the cancer immunotherapy field, especially in the area of immune checkpoints. When the journal was first established in 2013, no agents targeting the programmed death (PD)-1 receptor or its ligand had been approved by the FDA and now checkpoint blockade has become a mainstay in the treatment of numerous malignancies.

Kidney cancer is one such disease for which checkpoint blockade has radically altered the treatment landscape, motivating SITC to update its Cancer Immunotherapy Guidelines. You can read the Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma by Brian Rini et al. in this issue.

And our understanding of immune checkpoints continues to progress. Almost every aspect in the translational research pipeline is represented in the manuscripts in this month’s digest, including characterization of the tumor microenvironment, pre-clinical validation for two novel checkpoint blockade strategies, and the first retrospective study of the tolerability of anti-PD-1 or anti-PD-L1 therapy in patients with pre-existing or newly diagnosed paraneoplastic syndromes.

With best regards,

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

To view the entire January 2020 JITC Digest, please click here

Tuesday, January 7, 2020

President's Message - January 2020

Dear Colleagues,

In my December President’s Message, I outlined our society’s future ambitions, focused on six strategic goals through 2021. This month, I’d like to describe some of the programs and initiatives to achieve those strategic goals.

SITC strives to be the most comprehensive and reliable resource for information and education on cancer immunotherapy. One way in which our society serves the greater cancer immunotherapy field is through our open access, peer-reviewed Journal for ImmunoTherapy of Cancer (JITC). The quality of research presented in the journal has grown over the years and it is now arguably the top journal focusing on cancer immunotherapy. Given this growth, SITC officially transitioned JITC to a new publisher this month, BMJ, giving JITC the optimal platform to engage readers, authors and the greater field of tumor immunology and cancer immunotherapy. Learn more in this special editorial from JITC Editor-in-Chief Pedro J. Romero, MD.

SITC is invested in developing the next generation of leaders in tumor immunology and cancer immunotherapy. To further this mission, we will offer five SITC Fellowship Awards in 2020, providing a total of a half-million dollars in funding opportunities to promising young investigators. The submission period for these funding and award opportunities is Jan. 21–March 2, 2020. Thank you to our industry partners who help make these annual award opportunities possible as we work together to develop the future leaders in the field.

The Women in Cancer Immunotherapy Network (WIN) Leadership Institute is another successful leadership development program that will grow in 2020. The 2019 WIN Leadership Institute held this past August hosted more than 60 emerging female leaders in the field. Because of the strong interest and demand for this program, and the overwhelming positive response to the first program, SITC will host two such events in 2020. I’m proud of SITC commitment to the professional development of women in the field, and I thank Immediate Past President Lisa H. Butterfield, PhD, for her role as a champion for the WIN initiative.

SITC’s main goal of improving cancer care and patient outcomes is reliant upon the commitment of time and expertise from our members from around the globe. The SITC Cancer Immunotherapy Guidelines are consensus-based clinical practice guidelines, developed by panels of experts, that help inform oncologists on when and how to use immunotherapy and how to manage the associated toxicities. SITC has now published seven different guidelines, including the recently updated consensus statement on renal cell carcinoma (RCC), which appeared in JITC in December. Five additional guidelines are currently under development and scheduled for publication in 2020.

Don’t forget to register for the free SITC webinar focused on the recently published RCC manuscript. Beginning at 11 a.m. EST on Tuesday, Jan. 7, this webinar will include an overview of the manuscript, and will review management of immune-related adverse events. Faculty will also be available for a Q&A session.

Also, please consider attending other SITC programs quickly approaching, including the Cancer Immunotherapy Winter School (Jan. 13–17 in Houston; onsite registration is available) and the Interrogating the Tumor-Specific Surfaceome for Immune Targeting workshop (April 23–24 in San Diego). Additionally, online registration is open for our upcoming Advances in Cancer Immunotherapy™ regional education programs in Charlotte, N.C., on Jan. 23, in Charleston, S.C., on Feb. 1, in Tucson, Ariz., on March 14, in Tampa, Fla., on March 21 and Seattle on March 28.

There are many other programs, initiatives, educational resources and more that SITC has planned in 2020 (here's a preview). I look forward to an exciting year ahead for our society and our members, and I hope to see you in a future SITC program in 2020.

Sincerely,















Mario Sznol, MD
SITC President

Thursday, December 19, 2019

JITC Letter from the Editor - December 2019


pedro-romero_1__1_.jpgDear JITC Readers,

This is the final JITC digest of 2019, and we are ending the year on a historic note with December’s issue containing the most-ever papers published in a single month since the journal’s inception! It has been an exciting year for JITC, and we look forward to what the future holds as the immunotherapy field continues to expand and evolve.

The highlighted papers in this month’s JITC digest truly exemplify some of the most exciting areas of research in our field, spanning preclinical models to human trials and adding new insight into the contribution of the tumor microenvironment to disease progression and immunotherapy resistance as well as the development of novel immunotherapeutic agents.

Be sure to read the Editor Picks below about microenvironment-targeting therapeutics for the reprogramming of myeloid-derived suppressor cells and for the selective depletion of tumor-associated macrophages, gene-edited “off-the-shelf” CAR T cells for the treatment of glioblastoma, preclinical validation for a new checkpoint inhibitor target in ovarian cancer, newly described mechanisms of immunotherapy resistance in melanoma, a deeper understanding of the two types of secondary bone metastases in prostate cancer, and a phase 2 trial describing dendritic cell vaccines for prostate cancer that that induce clinically meaningful immune responses.

With best regards,

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

To view the entire December 2019 JITC Digest, please click here

Tuesday, December 3, 2019

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

Thursday, November 21, 2019

JITC Letter from the Editor - November 2019


pedro-romero_1__1_.jpgDear JITC Readers,

You are receiving this email in the weeks after SITC’s 2019 Annual Meeting and Pre-Conference Programs. This year’s meeting was a smashing success, truly highlighting the broad spectrum of basic science and clinical and translational research in immunotherapy. It is an exciting time for the field, and we are looking forward to possibly seeing some of the data presented at the meeting in upcoming issues of JITC.

Additionally, I am delighted to announce that Dr. Jason Luke, of the University of Pittsburgh Medical Center Hillman Cancer Center, has accepted the role of JITC’s social media editor! Dr. Luke will be managing the journal’s recently launched twitter handle. Be sure to take a moment to follow @JITCancer.

This month’s JITC digest exemplifies the interdisciplinary nature of immunotherapy research, with everything from basic insight into T cell metabolism and immunology to clinical trial results and next-generation sequencing.

“TLR9 acts as a sensor for tumor-released DNA to modulate anti-tumor immunity after chemotherapy” by Tae Hung and colleagues reveals new insight into how platinum-based chemotherapy can act as an immune adjuvant through innate immune danger-sensing pathways.

A review by Bridget P. Keenan et al., “Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response,” describes the delicate balance between protective immunity in the liver and pathological inflammation that may lead to cirrhosis, fibrosis and cancer.

Beatris Mastelic-Gavillet et al. elucidate how adenosine within the tumor microenvironment contributes to disease progression by metabolic suppression of effector T cells. The paper, “Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8+ T cells,” outlines potential biomarkers to monitor future immunotherapies targeting adenosine signaling.

In “Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma,” Indu Ramachandran et al. provide the first evidence for affinity-enhanced receptor engineered SPEAR T cells infiltrating solid tumors—a promising result for the treatment of synovial sarcoma and other malignancies that fail to respond to immune checkpoint blockade.

Finally, Zijun Y. Xu-Monette and colleagues undertake impressive and comprehensive ultra-deep sequencing to identify differential links between somatic hypermutation in immunoglobulin heavy and light chains and clinical outcomes in diffuse large B cell lymphomas in, “Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies.”

I hope you enjoy this issue!

With best regards,

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

To view the entire November 2019 JITC Digest, please click here

Monday, November 11, 2019

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.

Sunday, November 10, 2019

SITC 2019 Scientific Highlights - Nov. 9

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 9, 2019, sessions of the 34th Annual Meeting.



In vivo tracking of adoptively transferred T cells enabled by PET/CT

Flexible copper-64-nanoparticle-based cell labeling system allows for in vivo tracking of adoptively transferred T-cells by PET/CT

Abstract O1

A flexible system for radiolabeling and tracking adoptive cellular therapies was presented by Hólmfridur R. Halldórsdóttir, MSc (Technical University of Denmark). By labeling T cells in vitro using copper-64 ([64]Cu) micelles, which are self-assembled lipids, the team was able to noninvasively monitor the in vivo biodistribution of these radiolabeled cells over the course of 40 hours using positron emission tomography/computed tomography (PET/CT), and track their response to various therapeutic interventions.

Prior to in vivo imaging, the impact of micelles on T cells was tested. Viability and function of the T cells were not affected by the micelles. Throughout all in vivo studies, there was correspondence between the number of T cells in an organ and the measured radioactivity, indicating the cell tracking technique could provide accurate quantification. Following whole-body irradiation, elevated activity was noted in the thymus compared to non-irradiated mice, which is a well-known homing site for T cells after total body irradiation (4.6±0.1% vs 2.1±0.1% of injected dose, respectively). Tumors were also treated with a sustained release depot of TLR7 agonist, and, following this treatment, a higher accumulation of [64]Cu-labeled T cells was observed in the tumor tissues. This approach may therefore help elucidate the in vivo behavior of adoptive cellular therapies, without compromising their efficacy, which has immense implications for future monitoring of cellular therapies.
  

HER2-positive cancers may benefit from novel bispecific treatment

A phase 1 dose escalation study of PRS-343, a HER2/4-1BB bispecific molecule, in patients with HER2-positive malignancies

Abstract O82

Sarina Piha-Paul, MD (MD Anderson Cancer Center) presented an investigation of a HER/4-1BB bispecific, known as PRS-343, in patients with HER2-positive cancers. This dose-escalation study has evaluated cohorts from 0.0005 to 8 mg/kg in order to identify the safety profile of PRS-343 and to determine the dose for further studies. Measures of response and biomarkers were among the secondary objectives.

Fifty-three patients with solid tumors have been treated to date, and the minimal active dose was found to be 2.5 mg/kg. At and above this threshold, eighteen patients have been treated and are evaluable. In this patient group, significant expansion of the CD8+ T cell pool was noted after treatment with PRS-343, especially in the tumor microenvironment, in accordance with the proposed mechanism of action for PRS-343. This led to a disease control rate in these patients of 55%, including 2/18 patients confirmed partial response. Higher expansion of CD8+ T cells was found in responding patients over non-responders. The treatment was considered safe, with no serious adverse events or dose-limiting toxicities reported. The investigators are therefore continuing the further investigation of this first-in-class 4-1BB bispecific.
  

Front-line atezolizumab improves PD-L1+ NSCLC outcomes

IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) monotherapy vs platinum-based chemotherapy (chemo) as first-line (1L) treatment in PD-L1-selected NSCLC

Abstract O81

PD-L1-postive NSCLC patients were treated with either front-line atezolizumab or chemotherapy in the IMpower110 study, presented by Giuseppe Giaccone, MD, PhD (Weill Cornell Medicine). In this study, both squamous and non-squamous NSCLC patients were enrolled, and randomized 1:1 to atezolizumab 1200 mg Q3W or platinum-based chemotherapy for four or six 21-day cycles. As the primary endpoint, overall survival was tested hierarchically by PD-L1 status (highest to lowest expression).

Across both arms of the trial, PD-L1 expression was evenly distributed: 37% of all-comers were TC3/IC3. The majority of patients experienced treatment-related adverse events: 60.5% of atezolizumab patients and 85.2% of chemotherapy patients reported any-grade events, with grade 3-4 in 12.9% and 44.1% as well, respectively. In patients with the highest levels of PD-L1 expression (TC3 or IC3), after a median follow-up of 15.7 months, the overall survival was significantly improved (by 7.1 months) with atezolizumab treatment over chemotherapy (HR=0.595, p=0.0106). The statistical endpoints were not met in the pre-specified next analysis group of TC2/3-IC2/3, however, so further analysis could not be performed for significance at other PD-L1 levels. Front-line atezolizumab may therefore hold promise for further exploration in highly-PD-L1-expressing NSCLC patients, who appear to derive the most benefit in this front-line study.

Microbial colonization linked to colorectal cancer immune responses

Helicobacter hepaticus remodels the tumor immune microenvironment and reduces colorectal tumor burden

Abstract O69

Based on the hypothesis that intestinal microbiota may modulate immune balance, Abigail E. Overacre-Delgoffe, PhD (University of Pittsburgh) presented a preclinical study of microbiome manipulation in colorectal cancer (CRC) models. Colitis-associated CRC was established through AOM-DSS induction, and half of these tumor-bearing mice were colonized with Helicobacter hepaticus (Hhep) after tumor development. Lymphocytes throughout the digestive tract and tumor were analyzed using flow cytometry and confocal microscopy.

Colonization of CRC tumor-bearing mice with Hhep was found to significantly remodel the tumor microenvironment, leading to increased dendritic and Tconv cell infiltration, as well as a decreased Treg presence. This also led to reduction of tumor burden and extension of overall survival for those mice supplemented with Hhep. Using FISH, Hhep was found to colonize not only the normal colonic mucosa, but also infiltrated tumors themselves as well. The authors report that the bacteria also lead to Hhep-specific CD4+ T follicular helper cell (Tfh) infiltration, which may contribute to more efficient anti-tumor immunity, particularly due to the increased number of organized tertiary lymphoid structures in the tumors. Further investigation of the microbiome may in turn provide insight and potential therapeutic mechanisms for improving anti-cancer immune responses.

Biomarkers for immunotherapy responsiveness in sarcomas defined

Immune enrichment and functional T-cell receptor (TCR) frequencies predict response to immune checkpoint blockade (ICB) in selected fusion-associated sarcomas

Abstract O33

Biomarkers of response to immunotherapy for sarcomas were analyzed and presented by Akash Mitra, BS (MD Anderson Cancer Center). Sarcoma patients (alveolar soft part and synovial) were treated with combination durvalumab and tremelimumab, and an in-depth analysis of tumor tissues was performed. Whole-exome, RNA- and TCR-sequencing were conducted to explore correlates with response.

Unlike some other cancer types, tumor mutational burden was not correlated with outcomes in this study. Rather, many immune-related pathways were upregulated in responders, as KEGG pathway analysis indicated higher activity of T cell and B cell response pathways, as well as increases in PD-L1. B cell infiltrates were also more frequent in responding tumors in both pre-treatment and on-treatment biopsies. T cell clonality was inversely correlated with outcomes, with an increased diversity in responders, and a lower maximum productive frequency in responders as well. While further immune deconvolution and BCR sequencing studies are on-going, these genetic and immune signatures may provide greater insight into the immune responsiveness of sarcomas.

Il-35+ B cells play a role in pancreatic cancer progression

IL-35+ B cells regulates anti-tumor immune response in pancreatic cancer

Abstract O47

Bhalchandra Mirlekar, PhD (University of North Carolina - Chapel Hill) presented a study of the immunologic processes that contribute to pancreatic tumor immunotherapy resistance. This involved the use of both spontaneous and orthotopic murine pancreatic tumor models, using a model with B cell-specific genetic loss of IL-35. Combination therapy of IL-35 blockade and immune checkpoint blockade was explored to further elucidate the role of IL-35.

This study uncovered an important role for regulatory B cells in the promotion of pancreatic tumorigenesis. Specifically, this cell population produced IL-35 – a cytokine which has been indicated in the suppression of T cell responses both in autoimmunity and cancer. The study further indicated that only B cell-produced IL-35 was essential for this immunosuppression to occur. When pancreatic tumors from the IL-35 deficient mouse model were treated with anti-PD-1 therapy, regression of normally immunotherapy-resistant tumors was observed. These preclinical studies were also corroborated through analysis of patient pancreatic cancer samples, in which an IL-35+ B cell subset was found, and correlated with dysfunctional T cells. IL-35-targeted therapy may therefore be promising for pancreatic cancer, but the model is still slightly disparate from the actual clinical situation. 

Bispecific anti-PD-1 and CTLA-4 antibody demonstrates promise of lower toxicity

A phase 1 study of AK104, a tetrameric bispecific antibody that targets PD-1 and CTLA-4 in patients with advanced solid tumors

Abstract O30

A dose escalation and expansion study of a PD-1/CTLA-4 bispecific antibody was presented by Ben Markman, MBBS, FRACP (Monash Medical Centre). While combination treatments of individual PD-1 and CTLA-4-targeting antibodies have shown encouraging efficacy, they are also limited by severe toxicities. Therefore, this group hypothesized that the bispecific tetrameric form of AK104 may maintain that efficacy while limiting toxicity due to enhanced tumor specificity. Patients with several solid tumor types were enrolled and dosed between 0.2 and 10 mg/kg Q2W with AK104 with the goal of determining the safety, efficacy, and recommended phase two dose of the treatment.

The bispecific agent was found to have a Kd an order of magnitude better than that of ipilimumab and nivolumab, supporting its improved targeting avidity. Fifty-five patients have been treated with a median of four doses as of data cut-off, with the most at the 6 mg/kg level. Any-grade treatment-related adverse events were reported in 63% of patients, with 11% of patients experiencing a grade 3 reaction, both of which compare favorably to the traditional combination therapy. When patients were treated with doses of at least 2 mg/kg, the overall response rate was 24%, and the disease control rate was 44%. Increases in Ki-67, a proliferation marker, were noted in peripheral CD4+ T cells after treatment with AK104, supporting immune activation. While it remains early to compare the efficacy of AK104 relative to currently-approved combination therapies, the initial safety profile of this agent warrants further investigation.

Immunologic responses noted in vaccine-treated glioblastoma

Phase II trial of therapeutic vaccine consisting of autologous dendritic cells loaded with autologous tumor cell antigens from self-renewing cancer cells in patients with newly diagnosed glioblastoma

Abstract O22

A patient-specific vaccine for glioblastoma patients, AV-GBM-1, was tested in a phase 2 study presented by Daniela Bota, MD, PhD (University of California – Irvine). The technique involved establishment of a short-term cell line from tumor tissue excised at the time of surgery, production of dendritic cells from PBMCs, and development of the vaccine antigens from irradiated tumor cell lysate. Vaccination was performed following completion of standard optimal therapy (surgical resection, radiotherapy, and chemotherapy). The study aimed to achieve a 75% survival rate fifteen months after enrollment, which would represent a 50% increase over survival from current standard therapies.

Thirty-one of the planned 55 patients have begun treatment, with success rates of 46/48 for cell line establishment and 41/42 for development of a successful leukapheresis product. To date, twelve patients completed all eight doses, and five discontinued early due to progression. Immunological responses including Th1, Th2, and Th17 responses were noted in 60% of patients for whom this was measured, indicating promising immune activation with this technique. No notable toxicities have been reported, with all serious adverse events not attributed to the treatment. The study is still ongoing, but, given the encouraging immune activation indications and safety profile so far, the authors are enthusiastic about future results.