Abstract 3527: Novel bacteria strains, CJRS-10671 and CJRS-10672, enhance anti-tumor efficacy in LLC1 syngeneic model and humanized PDX mice model

Abstract

Abstract Background: Immune checkpoint inhibitor has emerged as remarkable therapeutic that improves the anti-cancer effect of patients. However, response rate is low in a large proportion of patients. The overall efficacy of immune checkpoint inhibitor therapy remains unsatisfactory. Recently, live biotherapeutic products (LBPs) have emerged as potential therapeutics to overcome the limitation of immune checkpoint inhibitor. Here, we demonstrated the efficacy of CJRS-10671 and CJRS-10672 in tumor bearing mice models. Methods: To evaluate anti-tumor effects, 109 CFU/mouse CJRS-10671 was administered via oral gavage twice daily (BID) alone or in combination with anti-PD-1 (10 mg/kg, QOD, i.p.) for 10 days in a Lewis Lung Carcinoma (LLC1) syngeneic tumor model. Tumor growth was measured by calipers 3 times per week. We analyzed immune cell profiles by flow cytometry. In lung squamous cell carcinoma patient derived xenograft (PDX) model,109 CFU/mouse CJRS-10671 and CJRS-10672 were orally administered twice daily (BID) alone or in combination with pembrolizumab (10 mg/kg, Q5D, i.p.) for 35 days. Tumor growth was measured by calipers 3 times per week. We analyzed immune cell profiles and single cell RNA sequencing. Results: In LLC1 syngeneic tumor model, CJRS-10671 alone suppressed tumor growth comparable to that of immune checkpoint inhibitor (anti-PD-1 antibody) only treatment group. Combined administration of CJRS-10671 and immune checkpoint inhibitor significantly suppressed tumor growth (p<0.05). We found that combination of CJRS-10671 with anti-PD-1 antibody increased the population of CD8+IFN-γ+ cells in splenocytes and tumor-infiltrating lymphocytes (TILs).In humanized PDX model, CJRS-10671 alone significantly suppressed tumor growth compared with that of vehicle control and pembrolizumab only treatment (p<0.001). CJRS-10672 alone suppressed tumor growth compared with that of vehicle control (p<0.001) which is comparable with the efficacy of pembrolizumab alone. Combined administration of CJRS-10672 and pembrolizumab further significantly suppressed tumor growth than pembrolizumab alone (p<0.01). None of the mice in pembrolizumab showed more than 75% tumor growth inhibition cut-off (TGI-75%). Fifty percent of the mice in CJRS-10671 single treated group showed over TGI-75%. The groups of pembrolizumab combination with CJRS-10672, pembrolizumab combination with CJRS-10671, CJRS-10672 alone were observed 25%, 20%, and 11.1%, respectively (>TGI-75%).We confirmed that administration of CJRS-10671 increased population of CD8+ central memory T cells in tumor. Also, TGI (%) directly related features were mostly antigen presentation and monocyte origin cells, especially macrophage in immune-profiling analysis. Furthermore, we observed that CJRS-10671 and CJRS-10672 were associated with signaling of damage-associated molecular pattern (DAMP) and especially CJRS-10671 was related to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling by single cell RNA sequencing analysis. Conclusion: CJRS-10671 and CJRS-10672, single administration or combination with anti-PD-1 antibody, have potential anti-tumor effect. Citation Format: Arim Min, Bo-eun Kwon, Hyunjeong Kim, Hyunkyung Park, Jiyoung Lee, Kyoung-Ho Pyo, Byoung Chul Cho. Novel bacteria strains, CJRS-10671 and CJRS-10672, enhance anti-tumor efficacy in LLC1 syngeneic model and humanized PDX mice model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3527.