Wednesday, September 27
Plenary Lecture 3: Cancer Immunotherapy: Checkpoint Inhibitors, Adoptive Cell Therapy, and Beyond
Samuel C. Blackman, Silverback Therapeutics, Inc.
The ability of the immune system to control or eradicate malignant cells has been known for over 100 years. However, it is only within the past 10 years that we have witnessed the successful development of a broad array of effective therapeutics that allow for the targeted manipulation of the immune system in a purposeful manner to treat malignant tumors. Although the era of cancer immunotherapy is in its relative infancy, it has already resulted in the FDA approval of multiple immune checkpoint inhibitors (ipilimumab, pembrolizumab, nivoluab, atezolizumab, avelumab, durvalumab), and cell therapies (spiuleucel-T, tisagenlecleucel). This initial generation of new therapeutics is being closely followed by multiple generations of novel therapeutic approaches and combinations.
Despite the great success of checkpoint blockade therapy, more than 50% of cancer patients fail to respond to monotherapy checkpoint inhibition or have sustained remissions. To address this gap, advances in genomics and proteomics, applied to both tumors and the endogenous immune response, at baseline and under the influence of current immunotherapies, are being utilized to search for new immune targets and accelerate the development of new therapeutics. We are witnessing the generation of vast quantities of data that are leading to an improved understanding of the adaptive immune response to tumors, the importance of the innate immune response in tumor immunology, novel mechanisms of immune resistance/escape, and the role of canonical cell signaling and cell metabolism pathways in the immune response to cancer.
This talk will provide an overview of the history of immunotherapy for cancer, with a focus on the development of checkpoint inhibitors, the “second wave” of new checkpoint inhibitors and immunostimulatory molecules. Also, the development and recent approval of chimeric antigen receptor T cells for B cell malignancies, and the “second wave” of new adoptive cell therapies under development will be included. Finally, a discussion of future directions for cancer immunotherapy will touch upon new targets beyond the T cell, as well current and emerging challenges in clinical development of cancer immunotherapeutics such as toxicity, cost, and the multiplicity of combinations.