APRIL 2023LIFE SCIENCES REVIEW8IN MY OPINIONPlease comment on your current role and responsibility in leading the cancer immunotherapy research and development at Janssen? I lead the immuno-oncology team at Janssen where our efforts are focused on the discovery and development of next-generation approaches to immunotherapy that include antibody-based drugs, cell therapies, and novel cancer vaccines. One especially promising approach that we are working on is allogeneic cell therapy, derived from induced pluripotent stem cells (IPSC). The objective is to convert these IPSC into immune cells that can fight cancer by engineering them ex vivo. This is incredibly significant as these stem cells can grow perpetually in culture, becoming a potentially inexhaustible source for treating cancer in a wider array of patients.What are some of the challenges you have witnessed in the cancer immunotherapy space, and how do you align yourselves accordingly?There are a number of challenges involved in bringing cancer immunotherapy to the patients that could benefit. One major difficulty is translating laboratory data into clinical data, i.e. predicting which agents will work in patients as our current models are reasonable, but far from perfect. Take for instance lymphocyte activation gene-3 (LAG-3), which was discovered as an immune checkpoint in 2004, showing that it was synergistic with anti-PD-1 in terms of anti-tumor effects. Those studies were performed in animal models in the first line setting. But when this drug was taken to the clinic, it was tested after initial therapies, i.e. mostly in the second and third line settings. So, its activity was not impressive. Finally, after many years, the clinical studies were aligned with the initial murine studies, i.e. the anti-LAG-3 / anti-PD-1 combination was tested in the first line in patients with melanoma. Those data were impressive, the combination doubled progression-free survival, leading to approval. On the other hand, there have been a fairly large number of trials in which promising laboratory results just did not pan out as expected. Take for example T cell immunoglobulin and ITIM domain, or TIGIT, where laboratory studies targeting TIGIT were quite impressive. Beyond that, a reasonably-sized randomized clinical trial in patients with lung cancer showed that anti-TIGIT combined with anti-PD-L1 may help treat lung cancer. Nevertheless, the larger, confirmatory (Phase III) trial was negative, for reasons that are really not clear. There are also some interesting examples showing mixed results. One of these involves a class of drugs designed to localize T cells to tumors and to activate them in the process. These go by many names, including bi-specifics, BITE's or T cell redirectors. They're fascinating molecules, marvels of modern genetic and protein engineering in which one arm of an antibody targets a tumor antigen, and the second is directed against T cells via CD3. In hematological THE CANCER IMMUNOTHERAPY TREATMENT PARADIGMBy Charles G. Drake, M.D., Ph.D., Vice President, Immuno-Oncology, The Janssen Pharmaceutical Companies of Johnson & JohnsonCharles G. Drake
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