adMare Global Leader Series featuring Dr. Tak W. Mak

Join us on Tuesday, March 25th at 12 p.m. ET, for an adMare Global Leader Series webinar featuring Dr. Tak W. Mak, Princess Margaret Cancer Centre, University of Toronto and Centre of Oncology and Immunology, University of Hong Kong. Dr. Tak W. Mak's starting point is that checkpoint inhibitors has accelerated the clinical implementation of a vast mosaic of single agents and combination immunotherapies.

However, the lack of clinical translation for immunotherapies as monotherapies or in combination emphasized the importance of discerning investigation. Multiple molecular mechanisms, such as metabolic alteration, genomic instability and neural regulation converge to propel tumour development are engaged. Mutations in enzymes, such as IDH, gives rise to gliomas, leukemia (AML) and lymphoma (AITL). Another component is a seemingly unconnected biological process and immunity is genomic instability. Unexpectedly, recent findings support the intriguing proposition that neurotransmitters, such as acetylcholine, tie the neuronal system to immune responses. I will discuss metabolic elements and neurotransmitters in immune cell regulation of infections, autoimmune diseases, liver regeneration and cancer development.

About Dr. Tak W. Mak

Tak W. Mak is internationally known for his work on the genetics and molecular biology of cancer and the immune system. He has been a major figure in the fields of immunology and molecular and cellular biology for almost 40 years, and is a world leader in basic and translational research into the genetics of immunity and cancer. In 1984, he led the group that cloned the gene encoding a chain of the human T cell receptor. This discovery laid the ground work for our understanding of much of T cell biology and heralded the CAR-T technologies now approved for the treatment of leukemias and lymphomas. Dr. Mak’s lab was also a pioneer in the genetic modification of mouse strains (“knockout mice”) to identify factors associated with susceptibility to immune disorders or various cancers. The Mak team used these mutant animals to elucidate the functions of numerous molecules involved in immune responses, programmed cell death, and tumorigenesis, including the important tumour suppressors p53 and PTEN, and the breast cancer-related genes BRCA1 and BRCA2. Notably, in 1995, his group used mutant mice to show that CTLA4 is a negative regulator of T cell activation, paving the way for the development of T cell checkpoint inhibitor regulators as immunotherapeutic agents. Dr. Mak’s laboratory continues to develop novel approaches for designing and producing TCRs that are specific for antigens appearing on the surfaces of cancer cells. In a different vein of investigation, his team recently showed that the brain communicates with the immune system via T and B cells producing acetylcholine, a finding with implications for future treatments of cancer and autoimmune or neurodegenerative diseases. The Mak group continues to uncover immune cell subsets that can synthesize this prototypical neurotransmitter, and is delving into the novel functions of this molecule outside neurotransmission.

In addition to this academic success, Dr. Mak has made significant contributions on the biotech front, in particular co-founding Agios Pharmaceuticals and Treadwell Therapeutics. These companies specialize in delineating metabolic vulnerabilities in tumour cells that can be exploited as novel cancer therapies. Several first-in-class small-molecule compounds are now in clinical trials for the treatment of cancer and certain genetic disorders. This strategy has produced two IDH inhibitors that are now FDA-approved for the treatment of acute myeloblastic leukemias, as well as another first-in-class agent for the treatment of anemia. Two novel agents targeting the aneuploid cancer cells common in advanced solid tumours are now in phase II clinical trials.

Dr. Mak is a member of the Royal Society of Canada, Royal Society of London, National Academy of Sciences (USA), American Society of Arts and Sciences (USA), and American Association for Cancer Research (USA). His copious accomplishments have been recognized by the scientific community through many prestigious awards and honours, including the Gairdner Foundation International Award (Canada), Emil von Behring Prize (Germany), McLaughlin Medal (Canada), King Faisal International Prize for Medicine (Saudi Arabia), Sloan Prize of the GM Cancer Foundation (USA), Paul Ehrlich and Ludwig Darmstaedter Prize (Germany), Novartis Immunology Prize (Switzerland), Gold Leaf Prize for Discovery (Canada), Albert Szent-Györgyi Prize for Cancer Research (USA) and the 2023 Pezcoller Foundation-AACR International Award for Extraordinary Achievement in Cancer Research. Dr. Mak holds a dozen honorary degrees from numerous universities in North America and abroad, and serves on the boards of many top-ranked scientific journals and biotechnology companies.