Abstract 2631: Enhanced anti-tumor effects by a combination approach of interferon-γ producing recombinant Bifidobacterium and anti-mPD-1 antibody in syngeneic mouse model
Authors: Seki Yuji , Shioya Koichiro , Kobayashi Satoshi , Shimatani Yuko , Fujimori Minoru , Taniguchi Shun'ichiro 
Published: July 2017

Cancer immunotherapies like antibodies targeting immune checkpoint molecules have resulted in an extraordinary success in cancer treatment. Still, large fraction of cancer patients doesn’t respond to the antibody immunotherapy and lots of patients are suffered from immune-related adverse events (irAEs) which sometimes cause discontinuation of the treatment. The above problems highlight the needs in the cancer immunotherapy for attempting various approaches like synergistic combination therapy to minimize adverse events and enhance efficacy.

Interferon-γ is a cytokine having antitumor activity and has been developed as an anticancer drug in multiple cancer indications but failed due to its limited efficacy and severe adverse events. In several publications, IFN-γ has been clarified to induce PD-L1 expression in tumors [1,2]. Upreguration of PD-L1 renders tumor resistance to cytotoxic T cell and it may cause the limited efficacy of IFN-γ therapy. Our preliminary experiments suggested that an intratumoral injection of purified IFN-γ and following addition with anti-murine PD-1 antibody showed significant tumor suppression, implying a combination effects of regional IFN-γ and immune checkpoint blockers.

Here in the present report, in an aim of decreasing adverse events, we have created recombinant Bifidobacterium, which is a non-pathogenic anaerobic bacterium to secrete IFN-γ specifically inside solid tumor, and then demonstrated the combination of IFN-γ producing Bifidobacterium and anti-murine PD-1 antibody significantly suppress tumor growth whereas each single treatment moderately contributes to tumor suppression in a CT26 bearing syngeneic mouse model. In addition, ELISA assay indicated that there are substantial IFN-γ detected in tumor tissue but none of them are detectable in blood on the Day 4 of treatment. All in together, combination treatment with IFN-γ producing Bifidobacterium and anti-murine PD-1 antibody offers a promising anti-tumor approach.

Reference:

1. Abiko K., Br J Cancer, 2015 Apr 28;112(9):1501-9. IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.

2. Mimura K., Cancer Sci., 2014 Oct;105(10):1236-44. Inhibition of mitogen-activated protein kinase pathway can induce upregulation of human leukocyte antigen class I without PD-L1-upregulation in contrast to interferon-γ treatment.

Citation Format: Yuji Seki, Koichiro Shioya, Satoshi Kobayashi, Yuko Shimatani, Minoru Fujimori, Shun'ichiro Taniguchi. Enhanced anti-tumor effects by a combination approach of interferon-γ producing recombinant Bifidobacterium and anti-mPD-1 antibody in syngeneic mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2631. doi:10.1158/1538-7445.AM2017-2631