The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of non-self and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses.
The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging nonclinical and clinical data suggesting that cancer immunotherapy is becoming a key part of the clinical management of cancer will be discussed.
Daniel S. Chen, MD, PhD, is the Cancer Immunotherapy Franchise Head in Product Development at Genentech/Roche and Adjunct Faculty in Medical Oncology at Stanford University. He received a BS degree in Biology from the Massachusetts Institute of Technology (1990), a PhD in Microbiology & Immunology (1996) and MD (1998) from the University of Southern California. Daniel completed an Internal Medicine Residency and Medical Oncology Fellowship at Stanford University (2003). He went on to complete a Post-doctoral fellowship with Mark Davis in Immunology, where he was a Howard Hughes Medical Institute Associate. He also ran the metastatic melanoma clinic at the Stanford Cancer Center from 2003-2006, where he continues to care for melanoma patients. In that time, he studied human anti-cancer immune responses pre- and post- cancer vaccination and cytokine administration to determine why anti-tumor immune responses were not more clinically effective. He received a U19 grant to develop better immunologic tools to interrogate human immune responses and ultimately patented the MHC cellular microarray to detect and functionally characterize antigen-specific T cell states.
Since joining Genentech in 2006, Daniel has focused on the clinical development of anti-angiogenic and immune modulatory targeted therapies in both early and late development, as well as the diagnostic tools to aid their development. He is a reviewer for Clinical Cancer Research and gave the keynote presentation at the AACR NCI EORTC Annual Meeting 2014. He has continued to publish with academic and Genentech collaborators in the field of cancer immunotherapy.