Intratumor injection of BCG Ag85A high-affinity peptides enhanced anti-tumor efficacy in PPD-positive melanoma

TL;DR

Injecting BCG high-affinity peptides into melanoma tumors boosts anti-tumor immunity in PPD-positive individuals.

Contribution

Demonstrates that BCG-derived peptides can activate memory T cells in PPD-positive individuals to enhance tumor killing.

Findings

BCG high-affinity peptides loaded onto tumor cells enhanced PBMC-mediated tumor killing in vitro.

Intratumor injection of BCG peptides improved anti-tumor efficacy in PPD-positive melanoma mice.

Combining BCG peptides with anti-PD1 antibody increased antitumor effects and PDL1 expression.

Abstract

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-A*0201 high-affinity peptides of BCG Ag85A protein (KLIANNTRV, GLPVEYLQV), and then, A375 melanoma cells and HLA-A*0201 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.

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