Dr. Shore on Immunotherapy Targeting PSA and PSMA in Biochemically Recurrent Prostate Cancer

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Institute, discusses immunotherapy targeting prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in biochemically recurrent prostate cancer.

Previously, investigators evaluated INO-5150, a DNA-based immune therapy that targets PSA and PSMA with or without plasmid-encoded cytokine adjuvant interleukin-12 (INO-9012) in a phase 1/2 trial. The treatment was well-tolerated and safe, with no treatment-related serious adverse events. In an analysis that was presented at the 2020 AACR Virtual Annual Meeting II, INO-5150 with or without INO-9012 was administered followed by electroporation with CELLECTRA® on day 0, and weeks 3, 12 and 24. Peripheral blood mononuclear cells were collected before and after treatment from a subset of patients (n=19) and stimulated with PSA or PSMA peptides, negative or positive controls.

Treatment with INO-5150 with or without INO-9012 drove the expansion of antigen specific T cells. Patients with immune reactivity by flow cytometry were more likely to have a higher frequency of PSA/PSMA specific T-cell receptors (TCRs) that expanded at least 10-fold over their pretreatment value. However, patients without immune reactivity also demonstrated expansion in TCRs. The results suggest that INO-5150 induced PSA/PSMA specific T cells and that TCR sequencing is a valuable tool for assessment of immune responses induced by immunotherapy. Although the approach may not be a full-proof way to avoid T-cell suppression, it could help delay the time to androgen deprivation therapy, concludes Shore.