Abstract 484P
Background
CD300 glycoproteins are members of B7 family and are known to be involved in various T cell immune responses. Recently, CD300c was suggested as a negative regulator of T cell immunity. However, its role and therapeutic potential in cancer immunity is yet to be elucidated. Here, we developed a CD300c-targeted immunotherapy which triggers a potent anti-tumor immune responses and enhance PD-1 immune checkpoint inhibitor activity in colon cancer.
Methods
CL7, a monoclonal antibody against CD300c was generated and systemically administered to CT26 tumor-bearing mice either with or without PD-1 blockade. Tumor growth was monitored and tumor tissues were examined with flow cytometry, multiplex immunohistochemistry, and Nanostring.
Results
CL7 potently inhibited tumor growth in CT26 mice in a dose-dependent manner. Nanostring immune profiling analysis revealed extensive immunologic reprogramming within the tumor microenvironment, following CL7 treatment. Especially, gene expressions related to dendritic cell activation, Th1 response, and T cell activation were significantly upregulated after CL7 treatment. Consistently, flow cytometric and histologic analyses revealed that CL7 activated intratumoral CD8+ T cells, while decreasing CD4+Foxp3+ regulatory T cells, thereby promoting anti-tumor adaptive immunity within the tumor. Moreover, CL7 repolarized tumor-associated macrophages toward anti-tumoral M1 phenotype. Since CL7 treatment upregulated tumoral Pd-1 and Ctla-4 expressions as a negative feedback, we performed combination immunotherapy of CL7 treatment and PD-1 blockade to further enhance anti-tumor immune response. Combination treatment resulted in a stronger suppression of tumor growth and longer overall survival compared to monotherapy, supporting the further clinical development of this combination.
Conclusions
Overall, our study demonstrated that CD300c blockade is a novel strategy to induce a strong anti-cancer immunity and strengthen the efficacy of immune checkpoint inhibitor in cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jae-Won Jeon, Chan Kim, Hong Jae Chon.
Funding
CentricsBio.
Disclosure
S.I. Lee: Financial Interests, Institutional, Member: CentricsBio, Inc. J. Yeom: Financial Interests, Institutional, Member: CentricsBio, Inc. J. Seo: Financial Interests, Institutional, Member: CentricsBio, Inc. J. Jung: Financial Interests, Institutional, Member: CentricsBio, Inc. J. Jeon: Financial Interests, Institutional, Advisory Role: CentricsBio, Inc. All other authors have declared no conflicts of interest.