Abstract 2255: Combination treatment of cancer cell-targeted photoimmunotherapy plus anti-PD1 leads to synergistic anticancer activity in an immunocompetent mouse model
Authors: Okamura Stephanie M. , Hsu Michelle A. , Bergeron Daniele M. , Solis Estela , Yadav Deepak , Fong Jerry J. , Heim Roger , Garcia-Guzman Miguel 
Published: August 2019

INTRODUCTION: Photoimmunotherapy (PIT) is a new cancer-targeted platform technology that utilizes a photoactivatable dye (IRDye 700DX) conjugated to a cancer-targeting antibody. Binding of the antibody- dye conjugate to cancer cells followed by photoactivation with nonthermal red light elicits rapid necrosis of the cancer cells bound to the antibody conjugate. In previous studies using immunocompetent mouse models, intratumoral innate and adaptive immune cell activation was observed after PIT treatment. We hypothesized that combination therapy with PIT plus anti-PD1 may enhance the activity of anticancer immune activation elicited by PIT treatments and in this study we evaluated the effects of the combination treatment in an immunocompetent mouse model.

METHODS: Immunocompetent mice implanted with CT26 tumor cells engineered to overexpress specific recombinant mouse antigens, received PIT treatment alone, anti-PD1, or combination therapy and were assessed for tumor growth inhibition and complete response rate. In animals achieving a complete response, the specificity of the response was evaluated by tumor re-challenge experiments. Animals with residual disease had their tumors excised and assessed for intratumoral immune activation. Splenocytes from treated animals were harvested and evaluated for cytotoxic activity against the cancer cells.

RESULTS: Of the mice that received combination treatment, 7 of 14 achieved complete response compared to 0 of 14 and 1 of 14 when treated with anti-PD1 monotherapy and PIT monotherapy, respectively. All tumor-free animals from combination treatment also rejected formation of new tumors following inoculation with the same tumor type (CT26), but not tumors from a different cancer cell type (4T1). Splenocytes derived from animals that received combination treatment had the greatest cytotoxic activity against CT26 cells when compared to single agent controls. In addition, splenocytes derived from animals that received combination treatment had increased total CD3+ CD8+ cells, as well as increased CD62L-CD44+ effector memory CD8+ cells, in comparison to splenocytes derived from animals that received single agent therapies.

CONCLUSION: In this study, combination cancer-targeted PIT plus anti-PD1 treatment in immunocompetent mice resulted in synergistic anticancer activity due to enhanced adaptive immune activation, as demonstrated by tumor rejection and increased systemic, tumor-specific cytotoxic T cells, and effector memory CD8+ cells. The results of this study warrant the clinical evaluation of combination treatment of cancer-targeted PIT plus anti-PD1 therapies.

Citation Format: Stephanie M. Okamura, Michelle A. Hsu, Daniele M. Bergeron, Estela Solis, Deepak Yadav, Jerry J. Fong, Roger Heim, Miguel Garcia-Guzman. Combination treatment of cancer cell-targeted photoimmunotherapy plus anti-PD1 leads to synergistic anticancer activity in an immunocompetent mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2255.