Newswise — NEW YORK, June 7, 2023 – The Cancer Research Institute (CRI), a nonprofit organization dedicated to harnessing the immune system’s power to control and potentially cure all cancers, will confer the prestigious 2023 William B. Coley Award for Distinguished Research in Basic and Tumor Immunology on Tak W. Mak, PhD, DSc, FRSC, of the University Health Network in Canada and the University of Hong Kong.
CRI’s highest scientific honor, this award recognizes Dr. Mak’s profound discoveries throughout his career that helped establish the foundations of T cell immunology. Dr. Mak is a long-standing member of the CRI Scientific Advisory Council and serves on the Postdoctoral Fellowship Review Committee.
Overall, his contributions have propelled the immunotherapy field forward in tremendous fashion, making many of today’s life-saving treatments possible. Most notably, Dr. Mak cracked a very important code: that of the T cell receptor (TCR).
In the 1980s, the biggest mystery in immunology was how T cells interact with target cells and their antigens. By correctly predicting the sequence of the TCR beta chain, Dr. Mak unraveled the blueprint for T cells' remarkable specificity with respect to recognizing antigens. This momentous achievement revolutionized our understanding of immune responses and laid the foundation for significant advancements in the field of immunology.
This paved the way for T cell therapies and deeper exploration of what makes these immune assassins tick. Soon, Zelig Eshhar, PhD—recognized by CRI with the 2019 William B. Coley Award—created the first early construct of what we know as chimeric antigen receptor (CAR) T cells by co-opting the signals sent by the TCR to trigger T cell activation. The first CAR T cell therapy was approved for leukemia in 2017, and six are now approved to treat patients with lymphoma and multiple myeloma as well.
Other promising T cell therapies utilizing customized, engineered TCRs are now in clinical trials for solid tumors normally resistant to immunotherapies.
Later, his work also helped uncover the roles of immune checkpoints like CTLA-4 in regulating T cell responses, aiding in the development of the first checkpoint inhibitor treatment.
After discovering the TCR's structure and function, Dr. Mak’s team concentrated on teasing out other crucial pathways governing T cell biology and behavior during immune responses, pioneering the use of genetically modified mice to do so. These efforts paid off in 1995 with the revelation that CTLA-4 acted as an immune checkpoint or ’brake’— finding that mice lacking it suffered from severe immune overactivation.
The following year, James P. Allison, PhD, the director of the CRI Scientific Advisory Council, capitalized on this insight by demonstrating that blocking CTLA-4 in mice enabled their T cells to kill their cancer. In 2011, Dr. Allison’s anti-CTLA-4 ipilimumab became the first checkpoint inhibitor approved by the FDA. Dr. Allison would go on to receive the 2018 Nobel Prize in Physiology or Medicine for this work.
CRI recognized the value of the work being done in Dr. Mak’s lab early on, first providing funding in 1985 and continuing to do so to this day. A CRI-funded CLIP Investigator himself from 2016-2018, Dr. Mak has sponsored sixteen CRI fellows in his lab over the last five decades.
“The CRI has always been a staunch supporter of our work, funding many of my lab’s postdoctoral fellows, without whom key discoveries would not have been made,” said Dr. Mak. “I will be proud to share the prestige of the William B. Coley Award with all of my lab team members and use this accolade to further boost our efforts to improve cancer immunotherapy.”
Most recently, two CRI-funded fellows in Dr. Mak’s lab — Julie Leca, PhD, and Shaofeng Liu, PhD — have helped him probe other factors governing T cell behavior, in the context of both cancer development and its immunotherapy-mediated elimination.
Earlier this year, Drs. Mak and Leca led work demonstrating that mutations in two genes, Idh2 and Tet2, were enough to promote the development of T cell lymphoma in mice. Specifically, the mutations induced aberrant behavior in follicular helper T cells (Tfh) that was characterized by irregular crosstalk with germinal center B cells.
Collectively, their findings suggest that targeting the interactions between Tfh and other immune cells within the tumor microenvironment could provide an effective therapeutic approach for patients with this disease.
Additionally, under Dr. Mak’s guidance, current CRI fellow Shaofeng Lui, PhD, is discovering how the neurotransmitter acetylecholine impacts the cancer-killing capabilities of T cells. Already, they’ve contributed to a study that uncovered a blood-based biomarker with immense potential value in the clinic.
Analyzing patients with a variety of advanced cancers who were treated with checkpoint immunotherapy yielded the finding that increases in the serum levels of choline, a precursor of acetylcholine, predicts patients likely to experience longer progression-free survival.
“Dr. Tak Mak reflects exactly the type of visionary scientist the Cancer Research Institute strives to empower,” declared Jill O’Donnell-Tormey, PhD, CRI’s Chief Executive Officer and Director of Scientific Affairs.
“Our deep belief is that by deciphering the basic principles of the immune system, we can bring its great power to bear against cancer. Dr. Mak’s work is an example of this philosophy in action. By decoding basic T cell biology, he opened up an entire new world of possibilities as far as treating cancer and numerous other diseases. We’re now starting to see the fruits of those contributions in a big way,” Dr. O’Donnell-Tormey added.
Dr. Allison also lauded the decision to bestow this award upon Dr. Mak.
“From his early work that determined the function of a variety of molecules involved in T cell development and function, his first cloning of the genes encoding human T cell antigen receptors, to his more recent studies linking the immune and nervous systems, Tak Mak has led the way in research in crucial areas of immunology. On top of all that, he has written a comprehensive textbook on immunology, been a leader in biotechnology, and served on many important advisory boards, including long-standing participation in the programs of the Cancer Research Institute.”
“Dr. Mak is richly deserving of this award,” he added.
Dr. Mak — a senior scientist at the Princess Margaret Cancer Centre, and a professor in the University of Toronto’s department of medical biophysics and the University of Hong Kong’s pathology department – will deliver the William B. Coley lecture on Wednesday, September 20, 2023 in Milan, Italy, where CRI with its partners, the European Network for Cancer Immunotherapy (ENCI) and the American Association for Cancer Research (AACR) will host their four-day International Cancer Immunotherapy Conference (CICON).
The award will be officially conferred by CRI at a ceremony to be held in New York City on November 6, 2023.
Prior to the Coley Award, Dr. Mak, whose research has been cited more 70,000 times, has received numerous awards and honors, including election into the Royal Society of Canada and the National Academy of Sciences.
About CRI
Established in 1953, the Cancer Research Institute (CRI) is a 501(c)(3) nonprofit organization dedicated to harnessing our immune system’s power to control and potentially cure all cancers. Our mission: Save more lives by fueling the discovery and development of powerful immunotherapies for all types of cancer. To accomplish this, we rely on donor support and collaborative partnerships to fund and carry out the most innovative clinical and laboratory research around the world, support the next generation of the field’s leaders, and serve as the trusted source of information on immunotherapy for cancer patients and their caregivers. https://www.cancerresearch.org
Cancer Research Institute is a registered 501(c)(3) nonprofit under EIN 13-1837442. Donations are tax-deductible to the fullest extent allowable under the law.
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