The Sentinel

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

Monday, March 29, 2021

March President's Message: Personal Reflections on Racial Disparities in Medicine and Research

 Dear Colleagues, 

I’m beginning this month’s President’s Message on a somber note. As many of you likely saw, our field recently lost a pair of luminaries in Giorgio Parmiani, MD, and José Baselga, MD. Dr. Parmiani, a 2008 recipient of SITC’s Smalley Award, served our society and worked with fellow members for decades, a few of whom shared thoughts in remembrance of Giorgio, which you can view here. Dr. Baselga, a targeted therapist whose chief area of research focused on breast cancer, served at a variety of academic medical institutions and companies over the years, most recently at AstraZeneca LP. Their contributions to science were vast and neither will be soon forgotten. Our thoughts are with their families and friends.

The passing of the noted Italian and Spanish researchers is a reminder that our connection within this scientific community is not limited by geographic boundaries. In fact, SITC members now represent more than 60 countries around the world, a number than has grown significantly in recent years. Inherently, and quite thankfully, this fact means that the SITC family features an increasingly diverse community of basic scientists, translational researchers and clinicians. Our society’s ability to seamlessly and graciously welcome new professionals from this global scientific community underscore the role we can play in breaking down walls to cultivate new relationships and create opportunities for scientists from all societal and cultural backgrounds.

Sadly, these concepts continue to be incredibly relevant in some very unfortunate respects. I am heartbroken by the recent acts of violence that have occurred against Asian Americans in the United States. My thoughts go out to all of those individuals, and their families, who have been hurt and/or affected by the actions of the hateful and uncaring.

As witnessed last summer during the Black Lives Matter protests, our country continues to reckon with the way it addresses racial inequities. As a young Asian boy growing up in West Virginia, it wasn’t always easy to see a future for myself in a true leadership position; CEOs and Presidents did not look like me. For decades, Asians have often been overlooked, particularly when considered for roles beyond the front lines of science and medicine. Even casual or professional conversations can feature micro aggressions or unconscious bias, which are damaging and ultimately limit or outright deter future professional growth. 

To achieve change, a community must raise their voices to have difficult issues acknowledged and addressed. From my experience, I see that it’s often too easy to sweep discrimination under the rug. It is why I was proud that on June 3, 2020, SITC published a statement in support of justice and equality. Simple as that may have seemed, it clearly communicates the society’s values and support for all individuals to achieve their full potential. 

Now, as our society’s first President of Asian descent, I will work with our members to shed light on existing inequities and find ways to address them that lead to tangible benefits for all. This year, SITC established a Diversity and Inclusion Task Force. Co-chaired by SITC Vice President Leisha Emens, MD, PhD, and SITC Board Member Adekunle Odunsi, MD, PhD, FRCOG, FACOG, this task force will focus on improving opportunities for research, education and professional development that promote diversity, equity and inclusion in SITC and the greater cancer immunotherapy field. 

SITC has a range of activities dedicated to early career scientists seeking to connect these young investigators at an early stage of their training to make new connections in the field and build their status within cancer immunotherapy research. Further, SITC is proud to offer a 2021 SITC Fellowship, made possible by an educational grant from Nektar Therapeutics, that focuses on equity and inclusion in cancer immunotherapy (applications are due by April 2 at 11:59 p.m. EDT, by the way). 

These are just a few ways in which SITC is working to address racial disparities in our field. I look forward to connecting with more of our members in the future to hear how we’re doing, and I’m also eager to continue the conversation in this space in the coming months, so be sure to follow along.

Sincerely,















Patrick Hwu, MD
SITC President

Thursday, March 25, 2021

SITC Remembers Giorgio Parmiani, MD

The Society for Immunotherapy of Cancer (SITC) remembers the life and scientific contributions of Giorgio Parmiani, MD. Dr. Parmiani brought his expertise to the society as a member in a number of ways, including serving on the World Immunotherapy Council and as an Associate Editor of the Journal for ImmunoTherapy of Cancer (JITC) from 2013–2019.

In 2008, Dr. Parmiani received the society’s highest honor, the Richard V. Smalley Memorial Award and Lectureship, and he delivered his keynote address at that year’s Annual Meeting titled, “Different Tumor Antigens in the Immunotherapy of Cancer: Are we Selecting the Right Target?” His research focused on the molecular characterization of human tumor antigens and the T cell response to them, significantly furthering our knowledge of cancer vaccines and anti-cancer immune responses. He was also a key leader in developing the Italian Network for Tumor Biotherapy, an organization that has contributed greatly to the field of cancer immunology and immunotherapy over the last few decades.

Dr. Parmiani was a beloved member of the SITC family, and several members below share further in his remembrance:

“Giorgio Parmiani, MD, PhD, was an internationally recognized scientist and physician who dedicated his life’s work to understanding the immune response to cancer and using it to improve outcomes of patients with cancer. During his tenure he trained a large number of scientists and physicians, and built a strong and robust group in Milan that continues to do amazing things. Giorgio was also a statesman who worked to unite much of the tumor immunology and immunotherapy community of Italy. He founded the Network Italiano per la Biotherapia dei Tumori (NIBIT) and served as its first President. Giorgio was a classic Milanese gentleman with great style who loved to host visiting colleagues in Milan. On one visit to his lab I remarked about the photos in his office of visitors who had come to visit at the Istituto Tumori. From our discussions it was clear that Giorgio was interested in the people who were the scientists and physicians in the field. In 2001 I was able to host Professor Parmiani as a Chiles Visiting Professor in Portland, Oregon. It was delightful and I was grateful to have our students, fellows and faculty interact with Giorgio and hear his perspective on the immune response against melanoma. However, for Giorgio it wasn’t only about cancer. It is hard for me to remember a time when we met where we did not discuss our spouses and children.

"I will miss Giorgio. He was a pioneering scientist and physician who had a great impact on the field of cancer immunotherapy, but he was also a kind and friendly heart that I admired for so many reasons.”Bernard A. Fox, PhD (Earle A. Chiles Research Institute, Providence Cancer Institute) 

“Giorgio was a teacher, a mentor, an example to follow. He was 'the immuno-oncologist' for all of us who were the believers in the field. If today there were an Italian school of oncologists dedicated to the field, it's his merit. He was also a father and, at the same time, a friend for us. He inspired all of our work with his research and ideas. This is a very sad moment for us. We should take his example as a model to inspire the new generation.”Paolo A. Ascierto, MD (Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale') 

“Giorgio was an example for me as young postgraduate of medicine; he was the type of translational researcher I was fascinated with. At that time and as many others, I was not sure that immunotherapy could have a bright future but his unwavering belief guided me. He actually put me in touch with Nick Restifo and helped to join his group at NIH. This experience changed my career for good and I truly owe Giorgio what I am today. Among his many activities, he founded the Italian network for immunotherapy and served as its first President. I will always remember his dynamic nature, the deep knowledge, and the fervent scientific discussions. We will all miss Giorgio.”Vincenzo Bronte, MD (University of Verona) 

Wednesday, March 17, 2021

Letter From the Editor- March


Dear JITC Readers,

Welcome to this month’s edition of the JITC digest. For many of our American and European readers, March marks the one-year anniversary of the first local shelter-in-place orders and travel restrictions in response to the COVID-19 pandemic.
 
Although everyday life is still far from the pre-pandemic normal in many places, it seems as though the news has been increasingly hopeful day-by-day, especially as the pace of vaccination continues to accelerate.
 
We in the immunotherapy community can share in some of the pride in the outstanding success of the RNA-based COVID vaccines—as JITC readers are well aware, the platform was originally developed for anti-tumor therapy. Additional intersections between cancer immunotherapy and SARS-CoV-2 will be explored in JITC’s new COVID-19 and Cancer Immunotherapy Review Series.
 
RNA vaccines are but one of many examples of innovations that originated in the immunotherapy field with far-reaching implications. Our discipline excels at developing new platforms, and there is no shortage of interesting technologies to be found in this month’s original research articles. As an example, be sure to read about the use of virtual clinical trials to optimize dosing schedules for combination oncolytic virus therapy in an intriguing computational biology paper by Adrienne L. Jenner and colleagues.
 
We have a wealth of biomarkers papers this month, all of which not only describe novel observations, but also rigorously provide mechanistic insight into tumor immunobiology. In one such report, Jiakai Hou et al elegantly leverage published data sets combined with a well-designed CRISPR/Cas9 drop-out screen to identify and categorize tumor-intrinsic resistance mechanisms to immune elimination.
 
Retrospective analyses also yield new insights in a paper by SIyuan Dai and colleagues, who identified in silico and validated in vitro a role for CD8+ T cell-secreted CXCL13 in immunoevasion by clear cell renal cell carcinoma.
 
A different chemokine’s receptor, CCR8 is revealed to be a specific marker of intratumoral regulatory T cells and a viable immunotherapeutic target that yields tumor control without autoimmunity in murine models in a manuscript by Helena Van Damme et al.
 
Finally, Karen Slattery and colleagues identify a novel, targetable and prognostic autocrine regulatory circuit involving TGF beta that leads to systemic natural killer cell dysfunction in patients with breast cancer.
 
Although many of us have been physically distanced from each other for much longer than we’d like, it is clear that our community of JITC readers, authors, editors, and reviewers is as strong and vibrant as ever, and I look toward the future with optimism.
 
Best regards,

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

To view the entire March 2021 JITC Digest, please click here

Tuesday, February 23, 2021

President's Message -- February Fireside Chat with BioNTech CEO Ugur Sahin, MD

 Dear Colleagues,

One of my hopes over the next two years as your society President is to have sit-down conversations with some of the leading experts in cancer immunotherapy, and even potentially, the greater global scientific field. These “fireside chats” will seek to celebrate the work accomplished by the individual (and his/her team) in cancer research, and discuss the ornate hurdles that remain present to any number of challenges in their line of work.

This month, I am extremely pleased to welcome SITC member, Ugur Sahin, MD. CEO of BioNTech SE, Dr. Sahin and his company collaborated with Pfizer Inc., to produce and receive emergency use authorization for a SARS-CoV-2 vaccine in record time. I spoke to Dr. Sahin this month, in my first fireside chat, to discuss his background as an academic professor and researcher, the obstacles his company has had to overcome to develop an extremely effective vaccine and his expectations for the months ahead as a billion or more humans seek to receive protection from this virus.

I’m featuring a portion of the Q&A below for this month’s President’s Message, but please visit SITC’s COVID-19 Resources page on SITC CONNECT to watch the entire discussion.

 

Question: How did you get this vaccine to U.S. FDA (emergency use authorization) in less than a year? Even the experts everywhere were saying it would take three to five years to get a vaccine initially, and here you did it in 11 months. How did you get that done?

Dr. Sahin: When we started our project, we expected this would really become a global pandemic. Our goal from the very beginning was to develop a vaccine and make it available in less than one year. We named our project Lightspeed, and the idea behind this designation was that we should not lose any time, so we did not have time to waste.

We implemented a 24/7 research program. When we started, we did not know what the best vaccine candidate was, so we started with 20 vaccine candidates. We did the full pre-clinical testing immunogenicity operation of these candidates. We even GMP toxicology study, because this was a pre-requisite from the Paul-Ehrlich Institute to evaluate that. We did the GMP manufacturing, and then we started the program just a few days later.

We submitted our documents on April 20 and three days later we had the approval to start the clinical trial in Germany. We did a partnership with Pfizer. Our plan was to have a serious approach to get all of the immunogenicity data from Phase 1. We understood that two vaccines provided really strong antibody and T-cell responses. We made the decision on July 24 for one of the candidates, and on July 27 the Phase 3 clinical trial started.

Question: What’s the future hold for RNA vaccines and infectious disease? Do you see that this technology is going to start to take over, and how many different epitopes can you put in there? Do you think you’re going to one day make a COVID-flu combination vaccine for example?

Dr. Sahin: The technology has extremely broad versatility, so you can combine. In our cancer trials, we are already combining four antigens, or six antigens. And this is of course possible in the same way for infectious disease vaccines. You can combine several antigens for one virus or combine antigens for different viruses.

Another key advantage of mRNA is to be able to make faster vaccines, so the manufacturing itself takes less than two weeks, then we have about two additional weeks for quality control and sterility testing, so that means you can in principle deliver a vaccine, from scratch, within four to six weeks. This is of course important advantages compared to the viral vector vaccines or the recombinant protein vaccines.

Question: How long do you think people will be immune for after having taken an RNA-based vaccine? Do you know from your cancer studies, can you predict with the COVID vaccine, is it going to be years?

Dr. Sahin: In principle we have to ask the question in different ways. The first lesson is what is needed to avoid infection at all? The prediction here is to avoid infection, you would need higher neutralizing antibodies, which are the key to avoiding infection. If you ask the question how long is protection for avoiding severe disease, this will be much longer. Avoiding severe disease can already be happening by having sufficient number of memory cells so that the immune response can kick on early, and even if you get infected, it’s not as severe disease because the immune system can catch up and control the virus infection in a few days. I think this is the way how vaccines work – if the immune response is quick, it can prevent severe disease; if the immune responses is very strong it can prevent infection.

Here at the moment in the pandemic situation, we are of course interested in both. First of all we would like to prevent infection, because if we prevent infection we will also prevent transmissions. But the second best thing we can do is prevent severe disease and thereby avoiding people dying from the infection. The latter could be accomplished, if the goal is the latter, then I believe such vaccines could have a memory effect for years. If we really want to avoid infection, then every year a booster might be useful.

 It was a very enjoyable and thought-provoking conversation, and I am very thankful for Dr. Sahin for his eagerness to share his experiences and lessons learned thus far from developing the coronavirus vaccine. I hope you enjoy listening to the entire discussion on the SITC website, and I look forward to other engaging fireside chats with cancer leaders in the future!

Sincerely,

 









Patrick Hwu, MD

SITC President

Wednesday, February 17, 2021

Letter From the Editor- February


Dear JITC Readers,

Welcome to the second JITC digest of 2021. The papers highlighted in this month’s spotlight exciting new frontiers in the immunotherapy field—underscoring the advancements made in new therapies beyond checkpoint inhibitors as well as the ever-evolving understanding of how the “classical” treatments exert anti-tumor effects.
 
The journal added new sections devoted to adoptive cell therapies and oncolytic viruses as recently as last year, and these important areas continue to advance.
 
This month, a paper by Jitendra Kumar et al reveals a strategy to overcome a longstanding challenge in adoptive cell therapies for solid tumors, namely, the immunosuppressive milieu in the tumor microenvironment. Additionally, Giulia Marelli and colleagues demonstrate a rational approach to enhancing the efficacy of oncolytic virus therapy with improved systemic distribution and enforced cytokine production for the vector.
 
The central role of the innate immune system in the anti-tumor effects of checkpoint inhibition are increasingly coming to prominence. Highlighting this rapidly evolving avenue of inquiry, Anastasia Prokopi et al provide evidence that dendritic cells are essential for tumor control in melanoma.
 
Complementing the original research in this month’s digest is an outstanding review by Xiuting Liu, Graham D Hogg, and David G DeNardo, which clearly outlines the direct and indirect effects of checkpoint inhibition on non-lymphoid cells. For additional nuanced and sophisticated explorations of the evolving landscape of tumor immune suppression and evasion, be sure to revisit the Immune Checkpoints Beyond PD-1 series.
 
Finally, it would be impossible for JITC to maintain its status as the preeminent immuno-oncology journal without the tireless efforts of anonymous peer reviewers, who ensure that every paper published in the journal is of the highest quality. In 2020, more than 1,400 unique reviewers evaluated papers for the journal, and the editorial board wishes to extend a sincere and heartfelt thank you for their dedication and perseverance. If you are interested in applying to become a reviewer, please visit the volunteer portal to apply.
 
Best regards,

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

To view the entire February 2021 JITC Digest, please click here

Monday, January 25, 2021

President's Message - January 2021

Dear Colleagues,

Happy New Year to all of you in the SITC family. This is my first message coming to you as SITC President and I find myself eager to begin as I assume a new role and our society continues to reach new heights. I would like to thank my friend and colleague Mario Sznol, MD, and all of the SITC Presidents before me, who helped SITC achieve such success to date, and I plan to continue such momentum in the coming two years.

As you know, we’ve all experienced many challenges in the past year. COVID-19 has upended all facets of our lives, but such conflict also pushed us to evolve and innovate in ways that allowed us to virtually congregate and collaborate to keep our society, and the greater cancer immunotherapy field moving forward.

One of the truly amazing things of this past year is, the solution to overcoming the pandemic through a safe and effective vaccine has been made possible as the result of advances in immunology. As the initial doses of the first approved vaccine were delivered to members of the general public in December, and as I recently received the vaccine as well, my heart swelled with pride knowing it was a cancer research company specializing in immunotherapies (BioNTech) that played such a crucial role in the development of this life-saving technology. Our field stands on the shoulders of countless giants in tumor immunology that have made today’s current state of care possible, and I know the future is bright as we continue our work to save and prolong the lives of all of our patients.

The coronavirus pandemic has reminded us all that regardless of how close-knit our local professional networks can be, we ultimately are all part of a larger, globally diverse field of cancer researchers and clinicians. This is part of the reason why SITC prioritized issuing a statement of support on FDA-authorized SARS-CoV-2 vaccines in December. As the statement notes, our society encourages all cancer patients receiving approved or investigational immunotherapy as part of their treatment regimen, either as standard of care or as part of a clinical trial and without a general contraindication to vaccination, to receive the vaccine when made available to them. The statement, published on Dec. 23, 2020, was done so by SITC leaders based on the known data at the time, and we will continue to monitor the field for any new information that could affect or further inform the society’s stance.

In 2020, our membership increased to more than 4,600 cancer immunotherapy professionals representing over 60 countries around the world. One of the key goals in our society’s strategic plan is to advance the science and application of cancer immunotherapy worldwide. As the SITC footprint grows with each passing year, it is incumbent upon our society to use this increased influence to broker new collaborations among scientific and governmental agencies all in an effort to improve patient access to new and promising therapies.

In December, SITC hosted the virtual workshop, Global Access to Cancer Immunotherapy: Closing the Gaps. Organized through the guidance and strategic vision of the SITC Global Access and Impact Committee, which is chaired by David Kaufman, MD, PhD, this workshop connected more than 60 stakeholders from around the world to discuss and define minimal infrastructure requirements for safe and effective IO administration around the world. Congruent with SITC’s mission to ensure that all immunotherapy advancements are accessible to the general public, enduring materials from this workshop are now available for your review.

Thank you to the countless individuals who helped make the past year a success for SITC, despite such difficult circumstances. I greatly look forward to working with so many SITC leaders and volunteers in the coming months as we continue our mission of improving cancer patient outcomes through immunotherapy. 

Sincerely,

 













Patrick Hwu, MD

SITC President

Wednesday, January 20, 2021

Letter From the Editor- January


Dear JITC Readers,

Happy new year and welcome to the first JITC digest of 2021. Even against the backdrop of the global COVID-19 pandemic, last year was a banner year for immuno-oncology, with immunotherapy becoming the standard of care in more and more disease settings. I look ahead to 2021 with optimism that the immunotherapy field will continue apace—providing lifesaving options for patients with cancer and advancing our understanding of the basic immunological mechanisms of tumor control.
 
During the month of December, four new papers from the Society for Immunotherapy of Cancer (SITC) were published in JITC, including the clinical practice guideline on immune effector cell-related adverse events, which will be of great value to the hematology and oncology communities. The journal is proud to support the society’s goal of scientific exchange by publishing these excellent peer-reviewed papers among the top-tier research that appears in JITC.
 
The original research articles highlighted in this month’s digest all provide new insight into one of the most challenging questions in our field: Why does checkpoint inhibition induce deep and durable responses in some, but not all, tumors?
 
Joshua R Veatch and colleagues develop an elegant enrichment and deep-sequencing strategy to show that neoantigen-responsive T cells were associated with tumor control in one patient with melanoma—shining light on a relatively minor contribution of self-antigen reactive T cells.
 
Expanding our understanding of potential immune checkpoints beyond PD-1 in virus-associated solid tumors, Isobel Okoye et al identify upregulation of the TIM-3 ligand galectin-9 as a marker of functional exhaustion and impaired T cell and natural killer NK cell responses.
 
The exhaustion phenotypes of T cells from primary and metastatic sites in ovarian cancers are clearly delineated by Galam Leem and colleagues, identifying 4-1BB costimulation as a potential means to reinvigorate defective immune responses in this setting.
 
Finally, in a provocative rebuke of the so-called “obesity paradox,” Shannon K Boi et al show that high body mass index is associated with worse outcomes with PD-1 inhibition for renal cell carcinoma in the real-world setting, and use mouse models to provide mechanistic insight into a role for IL-1 beta in diminished responses to therapy.
 
With best wishes for the coming year,

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

To view the entire January 2021 JITC Digest, please click here