ASCO 2022: Future Targets for Cellular Therapy in Prostate Cancer

( In his portion of this case-based discussion, Dr. Narayan discussed some of the barriers to the efficacy of CAR-T therapies. These include limited T-cell expansion or persistence once infused, dysfunction of infused T-cells, tumor immune escape by down-regulation of the targeted tumor antigen, and inflammatory toxicities such as CRS or neurotoxicity.


ASCO 22_Vivek Narayan, MD, MS_0 


There are also unique challenges for this therapeutic modality in prostate cancer. Prostate cancer tends to metastasize to the bone, which can impose physical and immunologic barriers to effective T-cell redirection. Prostate cancer patients are often older, and their comorbidities can raise issues for immune cell function and clinical management of inflammatory toxicities.

ASCO 22_Vivek Narayan, MD, MS_1 


Dr. Narayan then shared recently published data from his own institution of a PSMA-redirected CAR-T cell therapy, which did seem to have some clinical impact. Spatial proteomics of samples tumor microenvironments showed both upregulation of T-cell proliferation markers, as well as potential resistance mechanisms such as upregulation of immunosuppressive signals like PD-L1 and IDO-1.


Dr. Narayan summarized thoughts on how to overcome barriers for T-cell redirection in prostate cancer and other solid tumors. There are numerous efforts underway to overcome challenges within a heterogeneous or immunosuppressive microenvironment, improve CAR-T cell persistence and function, improve antigen selection, and mitigate toxicity.


ASCO 22_Vivek Narayan, MD, MS_2 


Finally, Dr. Narayan compared and contrasted the two different T-cell redirecting therapeutic modalities covered in this case panel. These are summarized below.


ASCO 22_Vivek Narayan, MD, MS_3 


Presented by: Vivek Narayan, MD, MS, University of Pennsylvania

Written by: Alok K. Tewari, MD, PhD, medical oncologist at the Dana-Farber Cancer Institute, @aloktewar on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.