Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, 210008, China.
Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Cancer Immunol Immunother. 2024 Apr 17;73(6):103. doi: 10.1007/s00262-024-03693-7.
As one of the scheduled immunization vaccines worldwide, virtually all individuals have been vaccinated with BCG vaccine. In order to verify the hypothesis that delivering BCG high-affinity peptides to tumor areas could activate the existing BCG memory T cells to attack tumor, we firstly predicted the HLA-A0201 high-affinity peptides of BCG Ag85A protein (KLIANNTRV, GLPVEYLQV), and then, A375 melanoma cells and HLA-A0201 PBMCs (from PPD-positive adults) were added to co-incubated with the predicted peptides in vitro. We found that the predicted BCG high-affinity peptides could be directly loaded onto the surface of tumor cells, enhancing the tumor-killing efficacy of PBMCs from PPD-positive volunteer. Then, we constructed PPD-positive mice model bearing B16F10 subcutaneous tumors and found that intratumor injection of BCG Ag85A high-affinity peptides (SGGANSPAL, YHPQQFVYAGAMSGLLD) enhanced the anti-tumor efficacy in PPD-positive melanoma mice. Along with the better anti-tumor efficacy, the expression of PDL1 on tumor cell surface was also increased, and stronger antitumor effects occurred when further combined with anti-PD1 antibody. For microenvironment analysis, the proportion of effector memory T cells was increased and the better treatment efficacy may be attributed to the elevated effector memory CD4 + T cells within the tumor. In conclusion, using the existing immune response of BCG vaccine by delivering high-affinity peptides of BCG to tumor area is a safe and promising therapy for cancer.
作为全球计划免疫疫苗之一，几乎所有人都接种过卡介苗（BCG）疫苗。为了验证向肿瘤区域递送卡介苗高亲和力肽可以激活现有的卡介苗记忆 T 细胞攻击肿瘤的假设，我们首先预测了卡介苗 Ag85A 蛋白（KLIANNTRV，GLPVEYLQV）的 HLA-A0201 高亲和力肽，然后将 A375 黑色素瘤细胞和 HLA-A0201 PBMC（来自 PPD 阳性成年人）添加到与预测肽的体外共孵育中。我们发现，预测的卡介苗高亲和力肽可以直接加载到肿瘤细胞表面，增强来自 PPD 阳性志愿者的 PBMC 的肿瘤杀伤效力。然后，我们构建了携带 B16F10 皮下肿瘤的 PPD 阳性小鼠模型，发现向肿瘤内注射卡介苗 Ag85A 高亲和力肽（SGGANSPAL，YHPQQFVYAGAMSGLLD）增强了 PPD 阳性黑色素瘤小鼠的抗肿瘤疗效。随着更好的抗肿瘤疗效，肿瘤细胞表面 PD-L1 的表达也增加了，并且当与抗 PD-1 抗体进一步结合时，会发生更强的抗肿瘤作用。对于微环境分析，效应记忆 T 细胞的比例增加，并且更好的治疗效果可能归因于肿瘤内效应记忆 CD4+T 细胞的增加。总之，通过向肿瘤区域递送卡介苗高亲和力肽利用现有的卡介苗疫苗免疫反应是一种安全且有前途的癌症治疗方法。
