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Six CRI-Funded Scientists on Dr. James P. Allison’s Impact on Their Lives and Careers

December 06, 2018

On Monday, December 10, James. P. Allison, Ph.D., director of the Cancer Research Institute Scientific Advisory Council and co-winner with Tasuku Honjo of the 2018 Nobel Prize in Physiology or Medicine, will receive the Nobel Medal and Diploma from King Carl XVI Gustaf of Sweden at a ceremony in Stockholm. Our earlier coverage highlighted Allison’s groundbreaking contributions that led to this well-deserved recognition, most especially his discovery of how targeting the CTLA-4 immune checkpoint pathway could help the immune system eliminate tumors as well as his subsequent work to turn this discovery into treatments for patients.

“It's a real honor to receive this award,” Allison notes in a new CRI video interview. “One of the more gratifying things has been to receive the recognition of my fellow scientists for what we've achieved.”

The Cancer Research Institute funded many of these collaborators while they worked under the mentorship of the latest Nobel laureate. As the momentous ceremony draws near, we spoke with six CRI-funded scientists who have worked in Allison’s lab to ask about their experiences and the impact he’s made on their lives and careers.

Sergio Quezada, Ph.D.

Dr. Quezada was a CRI-funded postdoctoral fellow in the Allison Lab at Memorial Sloan Kettering Cancer Center from 2005 to 2008, and was a CRI-funded investigator at University College London (UCL) Cancer Institute from 2011 to 2015. Currently, he leads the Immune Regulation and Tumour Immunotherapy Research Group and is a professor of Cancer Immunology and Immunotherapy at UCL Cancer Institute in London, UK.

Sergio Quezada, Ph.D.

How did you first come to know Dr. Allison, and what inspired you to want to work in his lab?

I wanted to do basic science with clinical impact in cancer immunology. Jim was at the time moving to New York City to start his new lab and he was looking for a cellular immunologist. When I heard about it, I immediately contacted him (and asked Randy Noelle, my Ph.D. supervisor and mentor at Dartmouth College to put in a good word for me). Jim agreed to meet me in his office at the old Kettering building in NYC before his lab moved. We could see the new Zuckerman building rising from his window. He shared his vision for cancer immunology and how important it was to link basic and translational science, and explained his reasons for the move. It was impossible to consider any other options after that. 

What were your first thoughts upon hearing that Dr. Allison had been named the recipient of this year’s Nobel Prize?

I felt immense happiness. Jim and the field deserve this prize. What has been accomplished since Jim first developed the concepts of immune checkpoints is just the beginning and this is the right time for it to be recognized. Of course, I can’t deny I feel also very proud of him and the fact that I was lucky enough to work with a Nobel Prize winner. Unbelievable!

What is the most important thing you’ve learned from Dr. Allison about being a scientist, and how has that helped you in your career?

Follow the data. Let the data speak, don’t over-interpret data. And that it is okay to reconsider a previous idea or notion based on solid scientific evidence. As far as helping to develop my career, well, besides the above key pillars he gave me absolute freedom, funding, and a lab with amazingly smart and hard-working colleagues. The best culture media ever.

The breakthrough that earned Dr. Allison the Nobel Prize led to one of immunotherapy’s first definitive successes, and helped establish the field’s scientific legitimacy. What are your hopes for the future of the field of immunotherapy?

As I said, this is just the beginning, all based on basic science from the discovery of CTLA-4 in 1985, to Jim’s seminal paper in the 1990s showing that CTLA-4 was a checkpoint that could be targeted with antibodies to promote tumor rejection in mice, to the later discovery and validation of the PD-1 checkpoint. We are talking about discoveries made 20 years ago, followed by clinical validation no more than 10 years ago. Since then, a large number of additional checkpoint pathways have been discovered and evaluated pre-clinically and clinically. This makes me think the future looks bright but challenging. We will not be short in tools, but we must make sure we are not short on science and biology. I’m looking forward to seeing the next 10 years in this field.

Stephen Mok, Ph.D.

Dr. Mok is a CRI-funded postdoctoral fellow (2016-2019) in the Allison Lab at the University of Texas MD Anderson Cancer Center in Houston, TX, where he is exploring how checkpoint immunotherapies influence memory T cell differentiation.

Stephen Mok, Ph.D.

How did you first come to know Dr. Allison, and what inspired you to want to work in his lab?

When I was a graduate student in Dr. Antoni Ribas' laboratory at UCLA, I came across several high-impact papers from Dr. Allison's laboratory. When his 2010 New England Journal of Medicine paper about anti-CTLA-4 ipilimumab was published, followed by the FDA approval of ipilimumab the following year, it was a pivotal moment in cancer immunotherapy. I was excited to work on checkpoint inhibitors and wanted the opportunity to work with an independent thinker like Dr. Allison.
 
What were your first thoughts upon hearing that Dr. Allison had been named the recipient of this year’s Nobel Prize?

I was nervous the night before the prize was to be announced, especially because I was with Dr. Allison at the CRI-CIMT-EATI-AACR Cancer Immunotherapy Conference in New York City during that time. Dr. Allison deserves this incredible honor, as he has spent decades studying CTLA-4. The basic science that he translated into the clinic has made an incredible impact on cancer patients.
 
What is the most important thing you’ve learned from Dr. Allison about being a scientist, and how has that helped you in your career?

One of the most important things I have learned from Dr. Allison is being persistent. Science is hard work, but Dr. Allison taught me the importance of staying focused and not giving up easily. When I would come across a problem in an experiment, thinking it didn’t work, Dr. Allison would say “No experiment ‘doesn’t work’. It just didn’t turn out the way we would expect. Now we need to work around that and find out why.” He is an inspiration and his wisdom has helped me throughout my postdoctoral career.
 
The breakthrough that earned Dr. Allison the Nobel Prize led to one of immunotherapy’s first definitive successes, and helped establish the field’s scientific legitimacy. What are your hopes for the future of the field of immunotherapy?

There are still a lot of unexplored areas in the field of immunotherapy. For example, the mechanisms of tumor relapse, long-term immunity of checkpoint blockade treatments, etc. I would like to continue to see which combination of treatments will mediate the most significant responses in patients, with the hopes of curing cancer. 

Tsvetelina Pentcheva Hoang, Ph.D.

Dr. Hoang was a CRI-funded postdoctoral fellow in the Allison Labs at the University of California, Berkeley, and Memorial Sloan Kettering Cancer Center from 2002 to 2005. Currently, she is the vice president of research & development at Marker Therapeutics in Houston, TX.

Dr. James Allison with CRI postdoctoral fellow Tsvetelina Pentcheva Hoang, Ph.D.

How did you first come to know Dr. Allison, and what inspired you to want to work in his lab?

I first met Jim in the summer of 1999 as a third year graduate student, during the American Association of Immunologists-sponsored graduate course in immunology on the University of California, Berkeley campus. He gave a lecture about the potential of the immune system to survey for and destroy cancer cells, and how ongoing research in his lab was focused on ways in which we can make it do that better. After I graduated from Johns Hopkins University, I interviewed with him for a postdoctoral position and was thrilled that I was able to join his team. Trying to figure out the mechanisms of CTLA-4-mediated T cell inhibition was exciting not just from a purely scientific perspective (which it was!), but also because it had the potential to actually make a difference to a patient’s cancer treatment.  

What were your first thoughts upon hearing that Dr. Allison had been named the recipient of this year’s Nobel Prize?

“Oh my God! I always knew he was going to win it one day—it’s so cool that ‘one day’ is today!”  

What is the most important thing you’ve learned from Dr. Allison about being a scientist, and how has that helped you in your career?

Some of the lessons that I learned from Jim are to never take anything people say for granted, that data speak for themselves, and that tough questions during lab meetings mean much smoother peer review down the line. Plus, I also learned that the best science is done when surrounded by smart, knowledgeable people who also know how to have fun—in and out of lab. 

The breakthrough that earned Dr. Allison the Nobel Prize led to one of immunotherapy’s first definitive successes, and helped establish the field’s scientific legitimacy. What are your hopes for the future of the field of immunotherapy?

Personally, I hope that immunotherapy will become first-line therapy for more and more cancers, especially now that we are developing newer immune-based therapies that can evolve as the cancer tries to evade them, and which are significantly less toxic than chemotherapy and radiation treatment, and far less invasive than surgery. I hope the time will soon come when we no longer have to chop off body parts, burn parts of the body, or make people sick for months in hopes of eliminating a cancer. Instead, we’ll use the immune system to destroy cancerous cells and keep them from coming back, the way it has dealt with pathogenic organisms for millions of years.

Katharina Kreymborg, Ph.D.

Dr. Kreymborg was a CRI-funded postdoctoral fellow in the Allison Lab at Memorial Sloan Kettering Cancer Center from 2011 to 2013. Currently, she is a principal scientist at the Roche Innovation Center in Zurich, Switzerland.

Katharina Kreymborg, Ph.D. as a CRI postdoctoral fellow wth her sponsor Dr. James Allison

How did you first come to know Dr. Allison, and what inspired you to want to work in his lab?

Fifteen years ago, when I started my career in cancer immunotherapy with my diploma thesis at the University of Tübingen (Germany), this field had still been at the outskirts of oncology. Today it is regarded as the breakthrough form of therapy to combat cancer. Having been part of this revolutionary development and witnessing its successes continuously reinforced my passion for cancer immunotherapy and with that the inspiration to work with Jim. Needless to say that Jim’s work, especially on CTLA-4, had been well known and I got familiar with this and other aspects of his work already during my diploma thesis. Later on, I got to know people who worked in his lab and were telling me about how he is as a person, that he not only works on exciting and relevant questions in cancer immunology, but is also a lot of fun to work with, and about the good atmosphere in his lab.

What were your first thoughts upon hearing that Dr. Allison had been named the recipient of this year’s Nobel Prize?

I was super excited and very happy for Jim! Not only for this very deserved prize, but for all his achievements that significantly contributed to cancer immunology getting the attention it deserves. Most importantly, it’s added an exciting and important piece of the puzzle to understand how the immune system works. Admittedly, I also felt a little mad with myself for having missed this year’s CRI conference during which it was announced! I hope this attention given to Jim and cancer immunology will aid the field even further.

What is the most important thing you’ve learned from Dr. Allison about being a scientist, and how has that helped you in your career?

Curiosity and persistence. Follow the science and be ready to be amazed! The experiences I made during my time in Jim’s lab as well as the stimulating and enriching interactions with other CRI scientists have helped me tremendously. I truly value my time as a CRI fellow and part of Jim’s lab and still benefit from the diverse and ample food for thought this time brought.

The breakthrough that earned Dr. Allison the Nobel Prize led to one of immunotherapy’s first definitive successes, and helped establish the field’s scientific legitimacy. What are your hopes for the future of the field of immunotherapy?

I hope that we gain a deeper understanding of the immunological processes and pathways underlying anti-tumor immune responses, then have the trust and patience to follow up on this and develop new and precise ways to intervene in order to develop curative and kinder therapies for patients.

Cenk Sumen, Ph.D.Cenk Sumen, Ph.D.

Dr. Sumen was a CRI-funded postdoctoral fellow in the Allison Lab at Memorial Sloan Kettering Cancer Center from 2006 to 2009. Currently, he is the director of business development of the BioProduction Division at Thermo Fisher Scientific in New York City.

How did you first come to know Dr. Allison, and what inspired you to want to work in his lab?

I had heard about the previous work of the Allison Lab when I was a graduate student at Stanford studying T cells, and would drop in to say hello to friends working there (fellow Stanford grads Pete Savage and Mike Curran) when I was visiting the UC Berkeley campus. We also had a brilliant postdoc, Max Krummel, who had trained with Jim in the lab and who mentored me very generously during my training. My PI, Mark Davis, was the first to clone the T cell receptor and I know many labs had competed for that achievement. Jim struck me as a fair and honest person, a “good sport” in the highly competitive, winner-take-all nature of science. He seemed to be a good person to work for, someone who can make things happen, and several years later I was looking for a second postdoc opportunity and to win a CRI fellowship, and I was happy that Jim could provide for both, as well as a great environment to freely pursue my passion in imaging T cells as they go about their business, with a focus on existing cancer models.

What were your first thoughts upon hearing that Dr. Allison had been named the recipient of this year’s Nobel Prize?

I was actually in bed and checking my LinkedIn feed in the morning when it popped up, and I immediately responded with a heartfelt congratulations in the form of a post and a picture of Jim sporting a fine beard from his Berkeley days. It received by far the largest views of any post I had on that platform, just showing how well regarded Jim is and how excited everyone was with his timely and well-earned “ultimate award.” We were smiling for days afterwards!

What is the most important thing you’ve learned from Dr. Allison about being a scientist, and how has that helped you in your career?

It was a privilege to work in the Allison Lab for three years, two of those with the generous support from CRI. Jim struck me as a person who does things his way and never gives up. I admired his focus and tenacity, as well as his ability to inclusively influence all types of people in order to get them to support common progress toward aims that are not just important for science, but ultimately for all of humanity in our admittedly helter-skelter progress towards a better world. Perhaps I wasn’t the most focused or tenacious postdoc in his lab (sorry Jim!), but what I learned from that experience I have been able to apply to my career in the science, technology, and business of getting advanced therapies into the market. Jim is a larger-than-life character—a force of nature to make things happen and bring lasting benefit to millions of cancer patients worldwide.

The breakthrough that earned Dr. Allison the Nobel Prize led to one of immunotherapy’s first definitive successes, and helped establish the field’s scientific legitimacy. What are your hopes for the future of the field of immunotherapy?

I would like to see more T cell therapies, engineered and otherwise, targeting different forms of cancer, especially solid tumors that end up “cold” for various reasons. I sincerely believe that CAR T cells have opened up an entirely new therapeutic modality and we will see soon see hundreds of cost-effective T cell therapies delivered in an outpatient setting with durable, safe outcomes. I would also like to see our political leaders on both sides get behind immunotherapy and science in general and, conversely, for them to support expanding scientific education to provide excitement and direction for our all kids to consider pursuing STEM careers. Jim serves as a grand inspiration to all of us, and many more to come!

Xingxing Zang, Ph.D.

Dr. Zang was a CRI-funded postdoctoral fellow in the Allison Labs at University of California, Berkeley, and Memorial Sloan Kettering Cancer Center from 2002 to 2005. Currently, he is the Louis Goldstein Swan Chair in Cancer Research; a professor in the Departments of Microbiology and Immunology, of Medicine, and of Urology; and a faculty member of the Cancer Center, Diabetes Research Center, and Center for AIDS Research at the Albert Einstein College of Medicine in New York City.

Dr. james Allison with CRI postdoctoral fellow XingXing Zang

How did you first come to know Dr. Allison, and what inspired you to want to work in his lab?

During my Ph.D. study at the University of Edinburgh, I started to know Jim’s great work on co-stimulation and its potential to develop new cancer immunotherapy, which inspired me to join Jim’s lab for my postdoctoral training.

What were your first thoughts upon hearing that Dr. Allison had been named the recipient of this year’s Nobel Prize?

 My first thought was: “Truly well-deserved and not surprised.” Jim’s work for the development of a revolution in cancer therapy is well-deserved for the Noble Prize. For a decade, I told my lab members and others this. On Oct 1, 2018, one of my former Ph.D. students sent me an email writing, “I TOTALLY remember you saying when I was in grad school that you thought Jim would win the Nobel Prize one day—you were right!”

What is the most important thing you’ve learned from Dr. Allison about being a scientist, and how has that helped you in your career?

The most important thing I have learned from Jim about being a scientist is to focus on the most important parts of science and to give back to society, which has shaped much of my career and the way I have run my own lab since 2008.

The breakthrough that earned Dr. Allison the Nobel Prize led to one of immunotherapy’s first definitive successes, and helped establish the field’s scientific legitimacy. What are your hopes for the future of the field of immunotherapy?

My hopes for the future of the field immunotherapy are: (1) to significantly increase the therapeutic response of cancer patients to immune checkpoint blockade and to make CAR-T cell therapy work in solid tumors; (2) to make immunotherapy more successful in other diseases such as autoimmune disorders, infectious diseases, and transplantation rejection.

Congratulations, Jim, from all of us at the Cancer Research Institute!

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*Immunotherapy results may vary from patient to patient.

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