Abstract 2513: Anti-tumor therapeutic effects in mice treated with Listeria monocytogenes (Lm)-LLO immunotherapy in combination with PD-L1

Abstract

Abstract Published reports have shown that Listeria monocytogenes (Lm) LLO immunotherapies can be combined with different cytotoxic modalities such as radiation, chemotherapy or immunotherapy for treatment of cancer. In a recent study, the combination of Lm-LLO immunotherapy (ADXS11-001) with an anti-PD-1 antibody significantly inhibited tumor growth and prolonged survival in animals. The combined treatment significantly increased the generation of antigen-specific immune responses in the periphery, and the infiltration of CD8 T cells into the tumor. These findings demonstrated that Lm-LLO immunotherapy combined with blocking of the PD-1/PD-L1 interaction was a feasible approach. The expression of PD-L1 by tumor cells serves as a protective function that can lead to suppression of tumor-infiltrating effector lymphocytes, thus allowing tumors to escape immune surveillance. We hypothesized that the combination of an Lm-LLO immunotherapy with an anti-PD-L1 antibody may potentially increase the therapeutic efficacy of either single agent alone and may be translatable to the clinical setting. To evaluate this hypothesis, a tumor regression study was initiated in a mouse model where established tumors were treated with ADXS11-001, PD-L1 antibody or combination ADXS11-001/PD-L1 antibody and tumor growth was monitored. In addition to tumor regression, serum samples were collected at different timepoints post-treatment to evaluate the changes in expression of various cytokines and chemokines using mouse inflammation map (Myriad RBM). The initial results indicated that the combination of ADXS11-001 and PD-L1 was better at controlling tumor growth kinetics than the single agent treatments. Serum cytokine analysis indicated treatment-related differences in the kinetics of cytokines and chemokines induced after single agent or combination treatments during different days of the study. Currently, we are evaluating the anti-tumor effects and immune responses generated in the periphery as well as in the tumor microenvironment. The results of this study will provide further insight as to the anti-tumor potential of combination of Lm-LLO immunotherapies with PD-1/PD-L1 specific antibodies. Citation Format: Poonam Molli, Anu Wallecha. Anti-tumor therapeutic effects in mice treated with Listeria monocytogenes (Lm)-LLO immunotherapy in combination with PD-L1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2513. doi:10.1158/1538-7445.AM2015-2513