Abstract 6641: In situ immunization with the TLR9-agonist CMP-001 enhances anti-PD1 therapy in head and neck tumors
Authors: Cheng Yinwen , Lemke-Miltner Caitlin D. , Chan Carlos H. , Salem Aliasger , Weiner George , Simons Andrean 
Published: September 2020

Abstract
Immunotherapy involving immune checkpoint inhibitors (i.e. anti-PD1) has shown promise for the treatment of head and neck squamous cell carcinoma (HNSCC). However, only a small subset of HNSCC patients respond to these therapies. Therefore, the identification of alternative immunotherapeutic strategies is necessary to improve HNSCC patient outcomes. CMP-001 is a novel toll-like receptor-9 agonist that consists of an unmethylated CpG motif-rich G10 oligonucleotide encapsulated in virus-like particles. In situ vaccination of CMP-001 is believed to activate tumor-associated plasmacytoid dendritic cells (pDCs) leading to tumor antigen presentation to T cells and anti-tumor T cell responses. This study is designed to investigate if CMP-001 would enhance HNSCC tumor response to anti-PD1 therapy in a human papilloma virus-positive (HPV+) tumor mouse model. C57BL/6 mice were subcutaneously inoculated with murine HPV+ mEERL HNSCC cells on both left and right flanks of each mouse. CMP-001 (100 µg/mouse) was administered intratumorally (i.t.) 3 times over the course of 1 week into the left tumor as a single agent and in combination with anti-PD1 (50 µg/mouse, intraperitoneally (i.p.)) 3 times per week for 2 weeks. Succinate buffer i.t. in combination with human IgG i.p. was administered as controls. The role of anti-tumor immune response due to CMP-001+anti-PD1 treatment was investigated by the depletion of NK cells, CD4+ and CD8+ T cells. Tumor growth, survival and immune cell recruitment was monitored and analyzed in response to drug treatment. Results showed that in situ vaccination of CMP-001 alone and in combination with anti-PD1 therapy induced tumor regression in the injected tumors and the regression of CMP-001+anti-PD1-injected tumors was durable. Additionally, CMP-001+anti-PD1 induced tumor regression at the distant sites which was not observed in the other treatment groups. CMP-001+anti-PD1 also significantly prolonged mouse survival compared with other groups. The anti-tumor effect of CMP-001+anti-PD1 was accompanied by increased DCs, macrophages, IFNγ+ CD4+/CD8+ T cells, HPV+ CD8+ T cells and activated NK cells in tumors and lymph nodes near the injected site compared with control. The therapeutic and abscopal effect of CMP-001+anti-PD1 therapy was partially abrogated by NK cell depletion and completely abrogated by CD8+ T cell depletion. These results demonstrate the synergistic anti-tumor efficacy of CMP-001 combined with α-PD1 therapy and warrants further study of this combination as a novel immunotherapeutic strategy for the treatment of HNSCC.
Citation Format: Yinwen Cheng, Caitlin D. Lemke-Miltner, Carlos H. Chan, Aliasger Salem, George Weiner, Andrean Simons. In situ immunization with the TLR9-agonist CMP-001 enhances anti-PD1 therapy in head and neck tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6641.