Evaluation of the antitumor activity of moronecidin (Piscidin)-like peptide in combination with anti-PD-1 antibody against melanoma tumor.

Abstract

Immunotherapy has changed the landscape of oncology over the last decade and has become a standard of care for various cancers. Researchers previously demonstrated that B16-F10 melanoma in C57Bl6 mice is resistant to immune checkpoint inhibitors. The goal of this study was to investigate how anti-PD1 antibodies functioned in combination with a new antimicrobial peptide (AMP) called moronecidin-like peptide (MLP). We studied the cytotoxic effect of AMP on the B10-F16 tumor cell line with the MTT experiment. The necrotic and apoptotic cells were determined by Presidium iodide (PI) /Annexin V staining and flow cytometry-based methods. Mice were inoculated subcutaneously with B10-F16 tumor cells in the mammary gland. Each group was sacrificed two weeks after the last injection to examine tumor-specific CD8+ T cell responses using flow cytometry. Annexin V and PI staining assay revealed that MPL significantly induces apoptosis in B16F10 cells. It should be noted that MLP in combination with anti-PD-1 improved antigen-specific T-cell responses synergistically (P=0.01) when compared with respective monotherapy. Furthermore, when compared with the respective monotherapies, combination therapy significantly controlled tumor growth in B10-F16 tumor cells and increased survival rate. Treatments with anti-PD-1 inhibitors alone had only a minor effect on tumor size, whereas combination therapy resulted in significant tumor growth control and increased animal survival. MLP therapy combined with anti-PD-1 antibody improves anti-tumor immune response in addition to inducing tumor cell apoptosis. As a result, the evidence suggests that intratumoral injection of MPL can improve anti-PD-1 antibody antitumor response.