The Sentinel

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

Wednesday, October 21, 2020

JITC Letter From the Editor -October 2020


Dear JITC Readers,

Welcome to the latest edition of the JITC digest. For many of our readers, especially in the United States, October is associated with Halloween—the seasonal mood hearkens back to the earliest days of immunotherapy, when many considered the concept of immunological control of tumors to be the stuff of “witchcraft.”

Now, of course, thanks to tireless efforts by clinicians and researchers as well as participation by patients in clinical trials, our understanding of tumor immunology has advanced by leaps and bounds. Concepts once thought to be spooky and mysterious such as immune checkpoints are now generally accepted as common knowledge. Every advance, however, also brings new areas of inquiry, and JITC will continue to publish the leading research in our field. The JITC’s corrected Impact Factor just released by Clarivate Analytics of 10.252 attests to the growing influence of the journal in a field that has taken center stage in oncology and immunology.

We also look forward to SITC’s annual meeting and pre-conference program, this year reimagined as an entirely virtual experience. The virtual meeting will be a one of a kind opportunity to hear from luminaries in our field as well as view presentations on the latest research. Find out more about registration here.

The original research articles featured in this month’s digest highlight several exciting emerging areas in immunotherapy. Elham Beyranvand Nejad and colleagues add a new angle into the important topic of mechanisms of immunotherapy resistance, with an in-depth characterization of the importance of the myeloid cellular component in the tumor microenvironment for preventing recurrence.

Efficient targeting of regulatory T cells in the tumor microenvironment has had limited success to date, but Francesca Zammarchi et al provide promising pre-clinical evidence that a CD25-directed antibody-drug conjugate may efficiently deplete immunosuppressive cells and strongly synergize with checkpoint inhibitors, allowing for robust disease control.

In an outside-of-the-box approach to improve yields for chimeric antigen receptor T cell manufacturing, Andrea Schmidts and colleagues developed artificial antigen presenting cells that improve over conventional bead-based reagents for T cell activation in several aspects. Of note, Schmidts et al modified the artificial antigen-presenting cells to disrupt expression of the lentiviral binding receptor and avoid “vector sink” during transduction using CRISPR-Cas9—the technology honored with the 2020 Nobel Prize in chemistry.

Immunotherapy in the neoadjuvant setting is an important and ongoing area of research. Although the trial of nivolumab and ipilimumab prior to surgery for resectable non-small cell lung cancer reported by Joshua E Reuss and colleagues was prematurely terminated due to toxicity, the findings underscore the importance of future research, especially on biomarkers to predict response to treatment.

Finally, in addition to the excellent original research in this month’s digest, it’s a pleasure to spotlight a review from the recently completed series on immune checkpoints beyond PD-1. If you have not read these outstanding reviews, be sure to browse the entire collection, in addition to the overview of TIGIT in immunotherapy highlighted in this month’s digest.
 
Warm regards,

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

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

Wednesday, October 14, 2020

JITC Review Series: Immune Checkpoints Beyond PD-1

Checkpoint blockade—therapies that disrupt the interaction between co-inhibitory receptors on T cells and their cognate ligands thereby blunting activation and proliferation despite antigen engagement—is a testament to the power of translational research. What began as a curiosity-driven inquiry into the mechanisms of immune tolerance has blossomed into a fourth pillar of cancer treatment, complementing the traditional triumvirate of chemotherapy, surgery, and radiation to provide remarkable benefits to thousands of patients.   

The discovery of immune checkpoints spurred a renaissance in immuno-oncology, with parallel efforts directed at translating known mechanisms of T cell inhibition into clinically available therapies as well as at the identification of additional targets.

In the past year alone, more than one dozen new approvals were granted in the US for immunotherapies targeting the PD-1/PD-L1 axis. With more than 3,000 active clinical trials evaluating these regimens, not only for advanced or metastatic disease but also in the adjuvant or neoadjuvant settings, the pace of approvals for checkpoint inhibitors is not looking to slow down any time soon.

Despite this unprecedented advancement, a large subset of cancer patients do not respond to PD-1/PD-L1-directed therapies. Additionally, only one approved therapy targets an immune checkpoint other than the PD-1/PD-L1 axis: the anti-CTLA-4 antibody ipilimumab. In recent years, it has become apparent that a panoply of additional signaling pathways modulate T cell activity, with distinct mechanisms outside the role of the PD-1 pathway in controlling ongoing localized inflammatory responses or the function of CTLA-4 in systemic self-tolerance. Some of these newly discovered checkpoints are already the target of numerous investigational agents in human trials and widely considered to be on the cusp of approval, as in the case of LAG-3.

Accumulated experience with the approved checkpoint inhibitors targeting the PD-1 axis has also enabled reverse translational studies that reveal new nuances of the immune landscape of the tumor microenvironment. In addition to the discovery of new co-stimulatory or co-inhibitory receptors and ligands, a prominent role for populations outside the lymphoid lineage has come to light in the activation or suppression of T cell responses, including the importance of innate immune cells and stromal cells for anti-tumor activity. Several of the novel checkpoints that have been discovered in recent years have also been demonstrated to play critical roles in innate-mediated anti-tumor immunity—an important and ongoing area of study for the immunotherapy field. 

Translating observations from pre-clinical models into usable therapies is not without challenges, however, and several investigational agents targeting novel immune checkpoints have, to date, yielded disappointing responses as monotherapies in randomized trials. Yet ongoing studies show hints of promising synergy between existing PD-1/PD-L1-targeting therapies and agents targeting novel checkpoints. Intriguingly, some new agents have demonstrated activity in tumor types generally thought to be weakly immunogenic, suggesting that expanding the repertoire of immune checkpoints could open up new settings amenable to immunotherapy.

Although the clinical development process for novel drugs may seem slow, especially in light of the urgent need for effective therapies for all-too-many still-lethal cancers, checkpoint inhibitors beyond anti-PD-1/PD-L1 agents are poised for a breakthrough. Industry has placed large bets on emerging checkpoints such as LAG-3, TIM-3 and TIGIT, and academia continues to advance the research pipeline.

This review series supports the ongoing momentum for investigation and clinical development of immune checkpoints therapies beyond the PD-1 axis. The articles highlight all aspects of the translational research pipeline—including pre-clinical rationale for novel targets, ongoing human studies, and high-level considerations for trial design. Readers from across the clinical-translational research enterprise will find value in these exceptional reviews. It is an exciting time for immunotherapy, and, with JITC, we are proud to move the field forward in this promising new direction.

Best Regards,

 

Ana Carrizosa Anderson, PhD    
Series Editor                 
                                               

Dario A.A. Vignali, PhD
Series Editor
                                                                                                     

President's Message - October 2020

Dear Colleagues,

Our society continues its preparations toward our fully virtual 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020), scheduled for Nov. 9–14, 2020. Please take note that the SITC 2020 meeting registration fee has been waived for ALL SITC members. You can become a member or renew your membership during the SITC 2020 online registration process.

Also, to accommodate for the COVID-19 impact on cancer immunotherapy research this year, the late-breaking abstract (LBA) submission period will be opened to everyone. SITC will not require an LBA application to be submitted beforehand. Previously submitted LBA applications will automatically be invited to submit a full LBA during the LBA submission period, Sept. 8-22, 2020, at 5 p.m. PDT.

In addition to the intense preparations for the Annual Meeting, the Society for Immunotherapy of Cancer continues to make progress on its objectives for this year. Educating clinicians on all aspects of cancer immunotherapy is one of our main objectives and directly serves the goal of improving patient outcomes. This past month the Certificate in Cancer Immunotherapy Program was launched, and is being offered online via our society’s SITC Cancer Immunotherapy connectED platform. The SITC certificate consists of eight learning modules all of which offer relevant education credits (CME, CNE, CPE and MOC).  After successful completion of the modules, the SITC Graduate in Cancer Immunotherapy (SITC-G) designation is granted and identifies a healthcare provider who has completed specialized training in cancer immunotherapy.

The first of eight modules, presented by Robert Ferris, MD, PhD (Director of the University of Pittsburgh Medical Center Hillman Cancer Center, long-time SITC member and past At-Large Director), is now online. It covers basic concepts of immunology, including innate and adaptive immune responses. The other seven module topics, which will be launched in the weeks ahead, include:

  • Basic Cancer Immunotherapy Concepts
  • Immune Checkpoint Blockade
  • Managing Immune Checkpoint Inhibitor Adverse Events
  • Other Approaches, including Cytokines, Vaccines, Immune Cell Engagers
  • Oncolytic Viruses and Intralesional Therapy
  • CAR T Cell and Cellular Therapy
  • Implementing Cancer Immunotherapy in Clinical Practice

SITC executive leadership, faculty and staff have put many months of effort in the planning and continued execution of this exciting new SITC program. I would like to thank all of those involved in the Certificate in Cancer Immunotherapy program, including Executive Director Tara Withington, CAE, and Past President Howard L. Kaufman, MD, FACS, both of whom championed this effort and the need for such a program for multiple years.

To learn more about eligibility requirements to earn your Certificate in Cancer Immunotherapy, please click here. SITC members receive a 20 percent discount on all Certificate in Cancer Immunotherapy modules, so if you haven’t yet, please be sure to join the SITC family to take advantage of this exclusive member benefit.

Sincerely, 











Mario Sznol, MD

SITC President

Wednesday, September 16, 2020

JITC Letter From the Editor - September


Dear JITC Readers,

It is a pleasure to welcome you to this edition of the JITC digest. A new academic year is getting underway for many of our readers, and regardless of the “new normal” imposed by COVID-19, the journal continues to publish groundbreaking research from across the immunotherapy field.
 
The articles spotlighted in this month’s digest exemplify how the immunotherapy field excels at bringing a new perspective to processes or therapies that might be considered familiar—thus advancing our discipline in novel and important new directions.
 
John C. Flickinger Jr., and colleagues creatively overcome the obstacle inherent in many cancer vaccine approaches of pre-existing host immunity to the adenoviral backbone by engineering a new chimeric vector.
 
By taking a new look at a familiar cytokine, Tal Kan et al provide evidence that IL-31 may induce anti-tumor immunity in breast cancer.
 
New immune response biomarkers that could help identify patients with melanoma who may benefit from combination radiotherapy and CTLA-4 blockade are described by Celine Boutros and colleagues. Additionally, evidence for safety and efficacy with retreatment with anti-PD-L1 therapy after discontinuation for reasons other than toxicity or progression is provided by Siddharth Sheth et al.
 
Although the results were negative for a first-in-human trial for a first-in-class, orally administered, selective dual inhibitor of IDO1 and TDO2, reported by Aung Naing and colleagues, the findings could set the stage for future studies of rational combinations of therapies targeting tryptophan metabolism and other immunotherapy agents.
 
Finally, a first-of-its-kind study by Pedro Barata et al demonstrates the feasibility of using a commercially available cell-free DNA assay to identify patients with advanced prostate cancer and microsatellite instability-high tumors who may benefit from pembrolizumab.
 
To further your reading this month, be sure to browse JITC’s Reading List, with an intriguing selection of papers drawn from the viral immunology world, selected by Dr. Howard Kaufman.

Best regards,

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

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

Tuesday, September 8, 2020

President's Message - September 2020

Dear Colleagues,

Sincerely,
Our society continues its preparations toward our fully virtual 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020), scheduled for Nov. 9–14, 2020. Please take note that the SITC 2020 meeting registration fee has been waived for ALL SITC members. You can become a member or renew your membership during the SITC 2020 online registration process.

Also, to accommodate for the COVID-19 impact on cancer immunotherapy research this year, the late-breaking abstract (LBA) submission period will be opened to everyone. SITC will not require an LBA application to be submitted beforehand. Previously submitted LBA applications will automatically be invited to submit a full LBA during the LBA submission period, Sept. 8-22, 2020, at 5 p.m. PDT.

In addition to the intense preparations for the Annual Meeting, the Society for Immunotherapy of Cancer continues to make progress on its objectives for this year. Educating clinicians on all aspects of cancer immunotherapy is one of our main objectives and directly serves the goal of improving patient outcomes. This past month the Certificate in Cancer Immunotherapy Program was launched, and is being offered online via our society’s SITC Cancer Immunotherapy connectED platform. The SITC certificate consists of eight learning modules all of which offer relevant education credits (CME, CNE, CPE and MOC).  After successful completion of the modules, the SITC Graduate in Cancer Immunotherapy (SITC-G) designation is granted and identifies a healthcare provider who has completed specialized training in cancer immunotherapy.

The first of eight modules, presented by Robert Ferris, MD, PhD (Director of the University of Pittsburgh Medical Center Hillman Cancer Center, long-time SITC member and past At-Large Director), is now online. It covers basic concepts of immunology, including innate and adaptive immune responses. The other seven module topics, which will be launched in the weeks ahead, include:

·         Basic Cancer Immunotherapy Concepts
·         Immune Checkpoint Blockade
·         Managing Immune Checkpoint Inhibitor Adverse Events
·         Other Approaches, including Cytokines, Vaccines, Immune Cell Engagers
·         Oncolytic Viruses and Intralesional Therapy
·         CAR T Cell and Cellular Therapy
·         Implementing Cancer Immunotherapy in Clinical Practice

SITC executive leadership, faculty and staff have put many months of effort in the planning and continued execution of this exciting new SITC program. I would like to thank all of those involved in the Certificate in Cancer Immunotherapy program, including Executive Director Tara Withington, CAE, and Past President Howard L. Kaufman, MD, FACS, both of whom championed this effort and the need for such a program for multiple years.

To learn more about eligibility requirements to earn your Certificate in Cancer Immunotherapy, please click here. SITC members receive a 20 percent discount on all Certificate in Cancer Immunotherapy modules, so if you haven’t yet, please be sure to join the SITC family to take advantage of this exclusive member benefit.
















Mario Sznol, MD
SITC President

Wednesday, August 19, 2020

JITC Letter From the Editor - August 2020


Dear JITC Readers,

Welcome to this latest edition of the JITC digest. The papers highlighted this month offer exciting perspectives on the current state of the immunotherapy field as well as promising future directions for research.
 
Clinical oncologists can find a comprehensive overview of approved and emerging immunotherapies for multiple myeloma, including some of the new CAR T cell therapies currently in development, in the newest clinical practice guideline from SITC, by Nina Shah et al.
 
Promising clinical data on the use of checkpoint blockade for prostate cancer is provided in an original research article by Julie N Graff et al. The paper is the first to demonstrate durable responses with PD-1 inhibition in a subset of prostate cancer patients.
 
The identification of biomarkers to predict response to immunotherapy remains an important and ongoing area of study for our field. Two papers in this month’s digest highlight the key role that tumor metabolism plays in determining outcomes after immunotherapy, offering potential biomarkers for future study.
 
David Chardin and colleagues identify tumor metabolic parameters as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) that are prognostic and predictive for outcomes after anti-PD-1 therapy for non-small cell lung cancer. Another immunometabolic biomarker is identified by Fangming Liu et al, who identify an association between FABP5-positive tumor infiltrating T cells and improved overall and recurrence-free survival in hepatocellular carcinoma.
 
New immunotherapeutic targets is another high-priority topic for research, and Marta TrĂ¼b and colleagues demonstrate promising in vitro anti-tumor properties with a novel fibroblast activation protein (FAP)-targeted 4-1BB agonist (FAP-4-1BBL).
 
Finally, do not miss an excellent review by Christopher A Chuckran et al of Neuropilin-1, which acts as a receptor ‘hub’ for sorting signals from diverse ligands to both promote regulatory T cell (Treg) stability in the tumor microenvironment and inhibit anti-tumor CD8+ T cell responses—the latest in the Immune Checkpoints Beyond PD-1 review series.
 
As always, you can also further your reading with highlights from other journals in JITC’s Reading List, selected this month by Claudia M Palena, PhD, of the NCI.

Best regards,

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

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

Monday, August 17, 2020

President's Message - August 2020


Dear Colleagues,

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