June President's Message: Mentoring a Generation of Researchers, a Conversation with Dr. Steven A. Rosenberg

Dear Colleagues,

Before I announce this month’s fireside chat companion, I wanted to make sure you all have had the opportunity to view the recently published diversity panel discussion on barriers to Asians and Pacific Islanders in medicine and research. This program, conducted in collaboration with the Chinese American Hematologic and Oncologist Network (CAHON) and the Indo-American Cancer Association (IACA), was completed in conjunction with the SITC Diversity and Inclusion Task Force’s efforts to raise awareness of barriers that exist within our field for under-represented minorities. Such conversations can be a tremendous learning tool for leaders in institutions around the world, and I look forward to our society continuing the discussion on this and other related topics into the future. Please click here to view the panel discussion.

June is Cancer Immunotherapy Month™, and I could not think of a better scientist and person to host for this month’s fireside chat than Steven A. Rosenberg, MD, PhD. Dr. Rosenberg is a Senior Investigator in the Surgery Branch at the National Cancer Institute with more than 40 years of experience. You can click the link in the preceding sentence to view his official biography, but as you all likely know already, Dr. Rosenberg is among the most influential scientists in our field’s history. He has been – and continues to be – a mentor to countless researchers through the years, including myself. To recognize his contributions to the field, SITC last year established the Rosenberg Scholars Award, an honor he and I discussed in our chat.

I pulled out a small portion of my discussion with Dr. Rosenberg and inserted below for the purposes of this message, but I highly recommend viewing the entire chat on the SITC YouTube channel here.

Myself: What do you think the future holds (for cancer care) 10, 20, 30 years from now? …What do you think the treatments will be then?

Dr. Rosenberg: So we’ve had surgery with us for over 2,000 years, there are Egyptian papyri that talk about cancer being cut out. We’ve had chemotherapy, which we date to chemical warfare research during the Second World War in 1942, where nitrogen mustard caused laboratory workers to be exposed accidentally, would develop lymphopenias that led to the first application of chemotherapy for cancer. Radiation therapy dated from the year after (Wilhelm) Roentgen discovered x-rays in 1895, so we’ve had these treatments around and they’ve constantly been improved over time, but these have been tiny improvements.

We’re confronted today still with the situation that tells us that if you have metastatic cancer from anyone of these solid epithelial tumors, you’re not going to be cured by anything that’s now available. But we have examples with checkpoint modulators, you can get durable responses, with immunotherapy durable responses, and I would imagine all three of those original treatments will continue to be improved.

The discussion featured a number of topics, including his background and interest in cancer research, the state of cancer vaccines, words of wisdom for young investigators and much more. I hope you all enjoy the conversation as much as I did. Thanks again to Dr. Rosenberg for joining for this month’s fireside chat.

Sincerely,

 

Patrick Hwu, MD

SITC President

April/May President's Message: ARPA-H and Cancer Moonshot: A Chat with NCI Director Dr. Ned Sharpless

 Dear Colleagues,

As I am sure many of you saw, U.S. President Joe Biden recently announced as part of his administration’s budget plans to make considerable investment in research. The budget includes a request of $6.5 billion for the creation of a new health agency, the Advanced Research Projects Agency-Health (ARPA-H). According to many news reports, ARPA-H would reside within the National Institutes of Health and have a major focus on cancer, among other diseases.

To gain a better understanding of ARPA-H and a host of other topics involving the state of cancer research in the U.S., I recently hosted National Cancer Institute (NCI) Director Norman E. “Ned” Sharpless, MD for a fireside chat. I enjoyed my chat with Dr. Sharpless, which included discussion of the effect SARS-CoV-2 and the pandemic have had on the NCI, the role immunotherapy is playing in the advancement of cancer patient care in the U.S., the role the NCI can play in supporting promising areas of research and much more.

 

 

Watch the Entire SITC Fireside Chat

I’ve pulled a small portion of our chat, transcribed and inserted below, but I hope you have the time to listen to the full discussion, which you can view here.

Myself: As you know, SITC is an immunotherapy organization, and we appreciate you’ve spoken at our national meetings before, so thank you for that. Tell us about the National Cancer Institute, your views on immunotherapy and the importance of immunotherapy in the treatment of cancer.

Sharpless: Now I really talk about this fourth modality that we have – chemotherapy this kind of classical cytotoxic chemotherapy, surgery, radiation and this whole new toolbox of immunotherapy approaches. I think a really important thing for the NCI is how to support the clinical trials in the development of these agents, which is complicated and a lot of the paradigms have to change, measuring things like response and resistance to immunotherapy agents as some of the traditional approaches don’t apply as you know. But also I think we really have to continue to fund the basic science that supports the basic understanding of the immune system and its interaction with cancer, is still an area that I think is fascinating biology, and some of the new technologies, like single cell sequencing and new medicinal chemistry approaches, are really impactful in that area. It’s exciting to wed these new technologies to a really important problem like tumor immunology.

I also think there’s a role for the NCI for certain kinds of support of the clinical development of certain kinds of agents. The pharmaceutical industry does a really good job of combining PD-1 inhibitors with other agents. That’s a trial that Merck and others do very well, maybe not a high priority for the NCI unless it’s a really complicated trial or complicated agent, but where think there is a possible need for more support for the National Cancer Institute is around cellular immunotherapy trials, which is still quite challenging because of the manufacturing, regulatory and compliance issues, so I think there is a place where if the federal government can help de-risk these technologies a little more, by showing that they work, and particularly allowing trials to be multi-institutional. A single institution study is not nearly as convincing as something that the same CAR construct that can be done in multiple places with beneficial effect. So I think that’s an area where the federal government has a specific role to facilitate a very important kind of clinical research in immuno-oncology.

I think the suite of activities at the NCI now is very robust. As you know, the Cancer Moonshot which began in 2017, has a major focus on cancer immunology, both in adults and children, both in basic science and translational and clinical work. I think it’s really an established modality now and it’s important that the NCI work with groups like SITC to advance that mission.

Thank you very much to Dr. Sharpless for dedicating his time to speak about a range of important issues. I know our society looks forward to finding new and engaging ways our organization can collaborate with the NCI in the future. I also hope we get to see and hear from Dr. Sharpless in person during the 36^th Annual Meeting & Pre-Conference Programs (SITC 2021), scheduled to take place Nov. 10–14 at the Walter E. Washington Convention Center in Washington, D.C., and virtually for those who cannot attend in person. I look forward to seeing the SITC family in D.C. this fall.

Sincerely,

Patrick Hwu, MD

SITC President

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

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.

Click here to watch the full interview

 

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

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

Q&A with SITC Vice Presidential Candidate Patrick Hwu, MD

In celebration of Cancer Immunotherapy Month™, we’ve asked SITC leaders to participate in a Q&A series for The Sentinel. We’ve asked them to briefly share why they entered the field, advice they’d share with early career scientists considering a career in cancer immunotherapy and more.

Please see below the Q&A from Patrick Hwu, MD, of University of Texas MD Anderson Cancer Center. Dr. Hwu is a 2018 candidate for SITC Vice President. Learn more about his candidacy here. Voting for the 2018 SITC Election takes place June 14–28, 2018.

1. What initially excited or intrigued you about the cancer immunotherapy field to choose this as your career focus?

When we get a viral infection, we can get very sick, but almost always fully recover. This powerful ability of the immune system to naturally cure viral illnesses has always intrigued me and encouraged me that applying this system against cancer could be impactful. In addition, the non-specificity and toxicity of current cancer therapies, such as chemotherapies, have always seemed unpalatable to me.  T-cells have the ability to distinguish normal peptides from mutated cancer-associated peptides that differ in merely one amino acid. This ability can enable anti-cancer therapies that have high efficacy and low toxicity. Even though immunotherapies in the early days were quite toxic, recent advances have allowed us to get closer to this dream of efficacious therapies without much toxicity. I routinely now have patients who travel to Europe and other distant places on vacation in between their outpatient treatments of immunotherapy. 

2. What advice would you share to an early career scientist contemplating a career in cancer immunotherapy?

Go for it!!  This is an exciting field.  I somewhat envy young investigators entering the field now. We know so much more than we knew when I was starting out, such as many of the immunoregulatory mechanisms of the body, and now have such great techniques like CyTOF and single cell RNA-seq to rapidly answer questions. Be curious, focused, and resilient. Many young investigators are intimidated by challenges with obtaining research funding. But there are in fact many more sources of funding now than traditionally in academia in years past. There is so much potential for us to make a great impact in cancer care, and we need as many talented young minds working on this as possible. Finally, don’t let anyone tell you something is impossible. In the early days, there were only a few of us who believed in immunotherapy and it is gratifying to see how many “converts” we have now.

3. What are three of the biggest hurdles facing researchers in the field, and how do you think they can be solved?

1. Moving immunotherapy responses beyond the common “immunogenic” tumor types.  In my opinion, this is largely due to the lack of sufficient CD8+ T-cells recognizing these cancers, i.e., lack of T-cell priming. This can potentially be solved using cancer vaccines, T-cell therapy and intratumoral immunomodulation, which are all very exciting and promising approaches.
2. Insufficient numbers of young investigators entering the field. Because of the challenges of funding, as well as the lack of enthusiasm for immunotherapy for many years in the past, there is a large deficit of talented, trained immunotherapy investigators. While this is starting to correct itself naturally, we need to move forward with urgency to train additional basic, translational and clinical investigators so we can fulfill the promise of immunotherapy to help the many cancer patients in need of better treatments.
3. Scalability with current approaches. Many of the most exciting current approaches towards immunotherapy, such as T-cell therapy and personalized vaccines, may have challenges with scaling treatments to the population in need in an affordable fashion.  There are many financial pressures on our current health care system, and biologists, engineers, politicians, and the business community must work together to bring these exciting therapies to the many people who need them.

4. What area of research has you most excited for the future of the field, and why?

I am most excited about the many ways we can prime the immune system to induce larger numbers of T-cells able to recognize cancers, many of which are considered “non-immunogenic.” While much of the field has focused on the release of immune checkpoint blockade, this will be ineffective if there is insufficient numbers of specific T-cells recognizing the cancer to begin with. Cancer vaccines, T-cell therapy, and intratumoral immunomodulation (for example, with TLR or STING agonists) are all very exciting areas with much promise. Combining these approaches in a rational way with other immunotherapies and targeted therapies also has much potential.