Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Cancer Immunol Immunother. 2020 Dec;69(12):2465-2476. doi: 10.1007/s00262-020-02634-4. Epub 2020 Jun 18.
Emm55 is a bacterial gene derived from Streptococcus pyogenes (S. pyogenes) that was cloned into a plasmid DNA vaccine (pAc/emm55). In this study, we investigated the anti-tumor efficacy of pAc/emm55 in a B16 murine melanoma model. Intralesional (IL) injections of pAc/emm55 significantly delayed tumor growth compared to the pAc/Empty group. There was a significant increase in the CD8 T cells infiltrating into the tumors after pAc/emm55 treatment compared to the control group. In addition, we observed that IL injection of pAc/emm55 increased antigen-specific T cell infiltration into tumors. Depletion of CD4 or CD8 T cells abrogated the anti-tumor effect of pAc/emm55. Combination treatment of IL injection of pAc/emm55 with anti-PD-1 antibody significantly delayed tumor growth compared to either monotherapy. pAc/emm55 treatment combined with PD-1 blockade enhanced anti-tumor immune response and improved systemic anti-tumor immunity. Together, these strategies may lead to improvements in the treatment of patients with melanoma.
Emm55 是一种来源于酿脓链球菌（S. pyogenes）的细菌基因，被克隆到质粒 DNA 疫苗（pAc/emm55）中。在这项研究中，我们在 B16 黑色素瘤模型中研究了 pAc/emm55 的抗肿瘤疗效。与 pAc/Empty 组相比，pAc/emm55 的瘤内（IL）注射显著延迟了肿瘤生长。与对照组相比，pAc/emm55 治疗后肿瘤中浸润的 CD8 T 细胞显著增加。此外，我们观察到 pAc/emm55 的 IL 注射增加了肿瘤中抗原特异性 T 细胞的浸润。耗尽 CD4 或 CD8 T 细胞会消除 pAc/emm55 的抗肿瘤作用。与单独治疗相比，IL 注射 pAc/emm55 联合抗 PD-1 抗体显著延迟了肿瘤生长。pAc/emm55 治疗联合 PD-1 阻断增强了抗肿瘤免疫反应并改善了全身抗肿瘤免疫。这些策略可能会改善黑色素瘤患者的治疗效果。
