Abstract B112: Combined therapy with an autologous tumor cells/bacillus Calmette-Guérin/formalin-based vaccine plus anti-PD-1 inhibitor enhances the antitumor response in a 4T1 breast cancer model

Abstract

Immune checkpoint inhibitors have shown satisfactory results in different types of cancer, such as lung cancer and melanoma. However, in breast cancer their benefit as a stand-alone treatment have not been robust, suggesting the need of combined therapies. In preclinical and clinical studies some checkpoint inhibitors have shown enhancement of cancer vaccines’ antitumor effects. Cancer vaccines represent a promising immunotherapy since they induce a specific long-term immune response against tumor antigens, leading to an effective tumor elimination with minimal side effects. Based on successful previous experiences using an autologous tumor cells/bacillus Calmette-Guerin (BCG)/formalin-based vaccine in breast cancer, we aimed to enhance its antitumor properties by combining it with anti-PD-1. We used a 4T1 breast cancer model in BALB/c mice, receiving four weekly injections of either Phosphate Buffered Saline (G1), 50 μg anti-PD-1 (G2), or the vaccine plus anti-PD-1 (200 µg autologous tumor cells, 0.0625 mg BCG, 0.02% formalin plus 50 μg anti-PD-1) (G3). In G3, the tumor arrest ability of anti-PD-1 was enhanced, showing a stronger antitumor response compared to G2. This response was characterized by a high infiltration of CD8+ T and PD-1+ cells, and a likely prevalence of CD4+ Th1 cells as suggested by a low T CD4/CD8 ratio. This led to a marked tumor elimination represented by nearly 70% of tumor necrosis, and a 3-fold reduction of both tumor volume and mitotic index. Interestingly, anti-PD1 seemed to successfully enhance an important part of the vaccine’s antitumor response, indicated by 50% less TAMs infiltration and 10% more necrosis, though not significantly improving the overall antitumor effect of the vaccine. These limitations of the combined therapy may be overcome by using a higher anti-PD-1 dose and administering the two treatments at different times. Furthermore, the positive and promising effects of applying both treatments individually and combined, plus the vaccine’s low-cost and simple preparation method, encourage us to continue this study. The vaccine should be evaluated in combination with other checkpoint inhibitors and/or other target-specific compounds that can lead to new, highly effective, less toxic, personalized breast cancer immunotherapies. Citation Format: Maria Jose Godoy Calderon, Eglys Gonzalez Marcano, Ana Federica Convit. Combined therapy with an autologous tumor cells/bacillus Calmette-Guerin/formalin-based vaccine plus anti-PD-1 inhibitor enhances the antitumor response in a 4T1 breast cancer model [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B112.