The Sentinel

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

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 September 2020 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 September 2020 JITC Digest, please click here