Effect Of Adenoviral P53 (Ad-P53) Tumor Suppressor Immune Gene Therapy On Checkpoint Inhibitor Resistance And Abscopal Therapeutic Efficacy.

e14610Background: Immune checkpoint inhibitors represent an important advance in cancer therapeutics. However, most cancer patients do not respond or become resistant to this form of immune therapy. Methods: We evaluated the ability of Ad-p53 to reverse immune checkpoint inhibitor resistance and induce abscopal effects in the immune therapy resistant murine B16F10 melanoma tumor model. To mimic clinical conditions of checkpoint inhibitor resistance, animals with established tumors were treated with anti-PD-1 before initiating Ad-p53 intra-tumoral therapy. Results: Anti-PD-1 had minimal therapeutic efficacy compared to control treatment. A statistical analysis of variance (ANOVA) comparison of tumor volumes revealed that the combined effect of Ad-p53 and anti-PD-1 treatment was synergistic and superior to either therapy alone (p = 0.0001). Surprisingly, there was a statistically significant abscopal effect with decreased growth of contralateral tumors not injected with Ad-p53. The Ad-p53 alone (p = 0.046) ...