Evaluation of a ConvitVax/anti-PD-1 combined immunotherapy for breast cancer treatment

Abstract

Breast cancer therapies using checkpoints alone have not been highly effective. Based on previous experiences using the ConvitVax, an autologous tumor cells/bacillus Calmette-Guérin (BCG)/formalin-based vaccine, in breast cancer and the potential success of combined therapies, we sought to ascertain whether the ConvitVax combined with anti-PD-1 enhances the antitumor effect in a 4T1 breast cancer model. Animals received four weekly injections of either PBS (G1), ConvitVax (200 μg cell homogenate, 0.0625 mg BCG, 0.02% formalin) (G2), 50 μg anti-PD-1 (G3), or ConvitVax plus anti-PD-1 (200 μg cell homogenate, 0.0625 mg BCG, 0.02% formalin, 50 μg anti-PD-1) (G4). Five weeks post tumor induction all mice were euthanized, tumors extracted and evaluated pathologically and by immunohistochemistry. The combination group (G4) showed 10% more tumor necrosis, greater infiltration of PD-1⁺ cells and lower infiltration of TAMs, evidencing that the combination of ConvitVax and anti-PD-1 can improve the antitumor effect of the vaccine. Using a higher anti-PD-1 dose and administering each treatment at different times could further potentiate the effect of our therapy. Given the vaccine’s low cost and simple preparation, its use in combination with checkpoints or other target-specific compounds may lead to a highly effective personalized breast cancer immunotherapy.