The METIOR Incubator and Educating the Next Generation of Immuno-Oncology Experts

by Saman Maleki, PhD

In August 2017, SITC brought together a group of 29 young researchers and physicians, from across the world, that were involved in various aspects of immunotherapy research to compete in a bold new program called “Sparkathon.” These people were divided into three teams and tasked to work together to develop a solution tackling the most pressing hurdles facing the fast-growing field of cancer immunotherapy. Each team was assigned a mentor with extensive science and business background and teams formulated their solutions to a business deck and pitched it to a group of SITC leaders, academics, and industry experts.

One of the teams set to address the educational challenge facing early-career researchers ­– from any background/sector – who want to enter the field of Immuno-Oncology. This novel educational program is named Mentoring for Early Translational Immuno-Oncology Researchers (METIOR) incubator. It brings together researchers from various sectors and backgrounds and educates them about Immuno-Oncology while developing a team-based multi-institutional project under the mentorship of immunotherapy experts from academia and industry. The METIOR incubator received $75,000 in seed funding from SITC to assist the establishment of their unique educational program. 

METIOR incubator selected ten participants from a pool of highly qualified applicants with various backgrounds in cancer research and assigned them into two teams: 1) team Checkpoints and 2) team CAR T-cell. Each team is currently working on two different projects that is directly linked to cancer immunotherapy. Participants met each other and their mentors at the first METIOR retreat at The University of Pennsylvania (Philadelphia) in March 2018. After two intense days of mentored brainstorming and project development, each team received $20,000 in seed money to work on their respective projects.

Team checkpoint seeks to identify biomarkers that are associated with the activity of endogenous retroviruses with double-stranded RNAs (dsRNAs) in ovarian cancer that might sensitize these tumors to checkpoint inhibitors.

Team CAR T-cell aims to build a centralized information platform (Virtual Immune-oncology Tissue Consortium, VITC) comprising of reference to clinical and pre-clinical samples with a focus on immunotherapy. This platform will be the first of its kind to efficiently consolidate immunotherapy resources across institutions into a searchable, interactive scientific network accessible to all researchers worldwide.

Teams have monthly teleconference meeting with their mentors and will meet again, in person, with their mentors in early September in London, Ontario for the second METIOR Incubator retreat. They will work on consolidating their ideas and preliminary results to shape a joint grant application with the goal of seeking major peer-reviewed funding. The last METIOR Incubator retreat would be at the SITC 33rd Annual Meeting in Washington, D.C. in November, where each team will present their progresses during the noon hour on Friday (TimIOs) and Saturday (METIOR). For a complete look at the Annual Meet schedule, click here.

Link to METIOR incubator: http://www.sitcancer.org/education/sparkathon/2017-cohort/projects/metior

Link to the Checkpoints team: http://www.sitcancer.org/education/sparkathon/2017-cohort/projects/metior/checkpoints

Link to the CAR T-cell team: http://www.sitcancer.org/education/sparkathon/2017-cohort/projects/metior/car-t

Acknowledgment:

Author wished to thank Ms. Alexandra Cadena and Dr. Sebastiano Battaglia for their proofreading of this article.

President’s Message – May 2018

Dear Colleagues,

The identification, standardization and validation of biomarkers will assist clinicians to identify the best cancer immunotherapies for patients and inform research scientists about the most critical areas of immunology for further investigation. Data from the last several years has shown the importance of checkpoint molecule expression, tumor mutation burden and CD8+ T cell infiltrate localization in tumors for patient outcomes, yet clinically validated, actionable biomarkers are not yet in hand. As many of you know, biomarker research has long been a research focus of mine and one reason I became a member of the Society for Immunotherapy of Cancer (SITC), as SITC shares this passion to advance immune biomarker science. 

 

I am proud to have been chairing the SITC Immune Biomarkers Committee, which is working at the forefront of biomarker research. The committee convened in 2014 to review the state of the field and identify challenges and opportunities still facing the community. At the time, the committee was comprised of four working groups (WG) dedicated to the following topic areas:

• WG 1 – Immunologic Monitoring, Assay Standardization & Validation
• WG 2 – New Developments in Biomarker Assays & New Technologies
• WG 3 – Assessment of Immune Regulation & Modulation Systematically (High Throughput Approaches)
• WG 4 – Prediction of Clinical Outcome Based on Baseline Measures

These hard-working teams published five white papers in the Journal for ImmunoTherapy of Cancer (JITC) – SITC's open-access, peer-reviewed online journal. Building on these efforts, the committee is ready to apply its members' expertise to shaping the future of the field.

The SITC Immune Biomarkers Committee is pleased to invite individuals from across academia, biotech, pharma, government and clinical research communities to our upcoming workshop, Immuno-Oncology Biomarkers: State of the Art, May 16 – 17, 2018, in San Francisco. This small and focused gathering will support cross-disciplinary cooperation across organizations to advance biomarker development, shape innovative new collaborations, and determine future projects of the committee in the coming years.

This Biomarkers Workshop takes place following two days of dynamic collaboration during the Cancer Immune Responsiveness Workshop (May 14 – 15, 2018), which will feature discussions on the role of host genetics and environmental modifiers in cancer biology, adaptive and innate immune mechanisms that initiate a therapeutic response, and the development of improved in vivo models for screening novel therapeutic strategies.

SITC is proud to organize and support meaningful, impactful collaborations involving participants from every expertise. These workshops are an excellent example of SITC's effort to better the field, and I look forward to seeing you in San Francisco!

Sincerely,

Lisa H. Butterfield, PhD SITC President

President's Message – January 2018

Dear Colleagues,

This month, I wanted to update you all on some of the ways that the society fulfills its mission. As a reminder, the mission of the Society for Immunotherapy of Cancer (SITC) is to improve cancer patient outcomes by advancing the science, development and application of cancer immunology and immunotherapy.

President's Message - December 2017

Dear Colleagues,

The past year has been one of significant scientific progress for the field of cancer immunotherapy and tumor immunology. Among the highlights:

• Pembrolizumab received U.S. Food and Drug Administration (FDA) approval for treating patients with MSI-H/dMMR-positive solid tumors, marking the first ever “tissue-agnostic” designation for any cancer therapeutic, defining disease based on biomarker status rather than tissue location
• CAR T cell therapies obtained initial FDA approvals for treating both DLBCL and B-ALL following very positive clinical trial results
• Cancer immunotherapies also continued to gain new indications by obtaining initial FDA approvals in hepatocellular carcinoma (nivolumab), Merkel Cell Carcinoma (avelumab), and gastric/GEJ cancers (pembrolizumab)
• Multiple cancer immunotherapeutics including nivolumab, pembrolizumab, durvalumab, avelumab, and atezolizumab became options for treating patients with bladder cancer

As we look ahead to 2018, the Society for Immunotherapy of Cancer (SITC) will continue to create opportunities for collaboration and scientific exchange for our growing membership base and beyond. Today, I’d like to single out two inter-connected workshops SITC has planned for May 2018 on biomarkers and cancer immune responsiveness.

Ten years after its inception, the SITC Immune Biomarkers Task Force will lead a two-day workshop to discuss critical next steps in biomarker science and assay development. Session topics will include best practices and validation; biomarker identification; data and specimen sharing and much more.

SITC’s newly-formed Cancer Immune Responsiveness Task Force will host a two-day workshop on topics that include tumor evolution in the immune competent host and the resulting immune landscape; identification of common pathways that should be targeted to understand and increase immunogenicity among silent or “cold” cancers and more.

The Annual Meeting & Pre-Conference Programs – which will take place at the Walter E. Washington Convention Center, Washington, D.C. in 2018 due to continued growth and excitement – will always be our society’s hallmark event. SITC hosts interim programs throughout the year to provide focused opportunities to move new developments and initiatives forward for improving cancer patient outcomes through the advancement of science and clinical application of cancer immunotherapy.

Both of the workshops mentioned will be open to the public. Stay tuned to SITC in the New Year for additional event information, including dates and location.

Sincerely,

Lisa H. Butterfield, PhD

SITC President

Get to Know Sentinel Author: Nils Rudqvist, PhD

Name: Nils Rudqvist

Rudqvist

Title: PhD

Employer: Weill Cornell Medicine

When and why did you become a SITC member?

I became a SITC member in 2016 when I joined the laboratory of Sandra Demaria at Weill Cornell Medicine. My background is in radiation physics/biology, so immunology was quite new to me. One main reason for me to join SITC was to develop the necessary skills and knowledge to become a successful investigator in the field of immuno-oncology.

SITC 2017 Scientific Highlights - Nov. 11

The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights from the Saturday programs (Nov. 11, 2017) of the 32nd Annual Meeting in National Harbor, Md. (Scroll to the bottom of this blog post to view the Glossary).

Dendritic cell acquisition of MHC I controls CD8+ T cell priming

Brandon MacNabb, BS (University of Chicago) presented data supporting the concept of MHC I antigen presentation by Batf3-lineage DCs as a critical component of CD8+-mediated anti-tumor response. Researchers initially generated H2-KbAB (MHC I+) and Kb-/-(MHC I-) C1498.SIY acute myeloid leukemia cell lines and subsequently engrafted C57BL/6 mice to determine the contribution of tumor cell MHC I presentation in CD8+ T cell priming. Initial assessment revealed reduced tumor growth in C1498.SIY KbAB mice compared to C1498.SIY Kb-/- mice. CD8+ T cell proliferation was also increased in KbAB mice compared to Kb-/- mice (p < 0.05). The observed C1498.SIY KbAB-dependent CD8+ proliferation was abolished in Batf3-/- C57BL/6 mice (p < 0.01). IFN-ϒ secretion was also decreased in Batf3-/- KbAB mice, suggesting that Batf3 initiates CD8+ priming. Transfer of autologous T cells from KbAB tumor-bearing mice offered complete protection from tumor growth in tumor-free mice. Conversely, autologous T cells from Kb-/- mice offered no such protection. Interestingly, DCs isolated from the TME and the tumor-draining lymph node in tumor-positive mice had increased KbAB MHC I expression (p < 0.001), suggesting DC acquisition of tumor-derived MHC I. Ex vivo experiments confirmed that migratory KbAB DCs are capable of CD8+ priming. These data reveal the importance of Batf3-lineage DCs and tumor-derived MHC I presentation in CD8+ T cell activation of anti-tumor response, providing insight into potential development of DC-oriented therapies. 

SITC 2017 Scientific Highlights - Nov. 10

The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights from the first day of the 32nd Annual Meeting in National Harbor, Md. (Scroll to the bottom of this blog post to view the Glossary)

Co-administration of novel anti-sMIC antibody increases anti-CTLA-4 therapeutic response in TRAMP/MIC mice (O22)

Jennifer Wu, PhD (Northwestern University, Chicago, IL) presented recently-published data investigating the efficacy of a novel antibody targeting the highly immunosuppressive human activation immune receptor natural killer group 2D (NKG2D) ligand, sMIC, with the goal of increasing anti-CTLA-4 therapeutic response. Using a TRAMP (transgenic adenocarcinoma of the mouse prostate)/MIC mouse model, Wu’s group found that mice with increased circulation of tumor-derived sMIC receiving anti-CTLA-4 had ~25% decrease in survival over 8 weeks compared to mice receiving placebo (p < 0.05), as well as an increased risk of immune-related colitis. TRAMP/MIC mice receiving anti-CTLA-4 in combination with anti-sMIC had reduced prostate tumor burden (~0.25g vs ~6g, respectively; p < 0.001), increased DC activation, enhanced TCR/CD3 signaling, and increased T cell clonality in tumor infiltrates compared to mice receiving anti-CTLA-4 alone (P < 0.05). CR was observed in 4/5 combination-treated mice for at least 120 days post-therapy, with no cases of immune-related colitis. These pre-clinical anti-sMIC/anti-CTLA-4 data align with clinical observations in patients with mCRPC, melanoma and multiple myeloma who have demonstrated improved responses to anti-CTLA-4 therapy if they develop sMIC autoantibodies during the course of treatment. These results suggest that sMIC may act as a predictive biomarker for anti-CTLA-4 response. Furthermore, including anti-sMIC antibodies in CTLA-4-targeted therapies may reduce irAES and increase treatment efficacy.

On Tap at SITC 2017 - Nov. 8, 2017

The Society for Immunotherapy of Cancer (SITC) is pleased to welcome our delegates to the 32nd Annual Meeting & Pre-Conference Programs! We are thankful for the throngs of member leaders and faculty who dedicated so many hours to ensure the SITC Annual Meeting continues being the premier destination for research in the field of cancer immunotherapy.

On Tap Today

Wednesday kicks off the week's proceedings with the first day of Pre-Conference Programs. Once attendees complete registration to pick up badges and materials, they'll be joining the following sessions:

Immuno-Oncology Biomarkers: Today’s Imperatives for Tomorrow’s Needs

8 a.m. - 12:30 p.m. / Cherry Blossom Ballroom

The SITC Industry Committee has developed a Biomarkers Fair to allow companies and interested academic investigators to present their latest technology. This forum will provide the opportunity for presentation of multiple biomarker development efforts by all sectors and stimulate interactions between biomarker diagnostic innovators with each other and with end-users.