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