Treatment with INO-5150 +/- INO-9012 in PCa patients drove the expansion of a diverse pool of antigen specific T cells with a high Shannon’s Entropy value suggesting high TCR diversity. Patients with immune reactivity by flow cytometry were more likely to have a higher frequency of PSA/PSMA specific TCRs that expanded >10 fold over their pre-treatment value; however patients without immune reactivity also demonstrated expansion in TCRs. These data 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 that does not bias towards a specific T cell function.
over 4 years ago
Clinical • Late-breaking abstract
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PD-1 (Programmed cell death 1) • KLK3 (Kallikrein-related peptidase 3)
INO-5150 is a synthetic DNA therapy that includes plasmids encoding for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and INO-9012 is a synthetic DNA plasmid encoding for interleukin-12 (IL-12). Immunogenicity was observed in 76% (47/62) of patients by multiple assessments. Analysis indicated that CD38 and perforin co-positive CD8 T cell frequency correlated with attenuated PSA rise (p = 0.05, n = 50).