Evaluation of the antitumor activity of moronecidin (Piscidin)-like peptide in combination with anti-PD-۱ antibody against melanoma tumor

Objective(s): 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 B۱۶-F۱۰ melanoma in C۵۷Bl۶ mice is resistant to immune checkpoint inhibitors. The goal of this study was to investigate how anti-PD۱ antibodies functioned in combination with a new antimicrobial peptide (AMP) called moronecidin-like peptide (MLP).Materials and Methods: We studied the cytotoxic effect of AMP on the B۱۰-F۱۶ 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 B۱۰-F۱۶ tumor cells in the mammary gland. Each group was sacrificed two weeks after the last injection to examine tumor-specific CD۸+ T cell responses using flow cytometry. Results: Annexin V and PI staining assay revealed that MPL significantly induces apoptosis in B۱۶F۱۰ cells. It should be noted that MLP in combination with anti-PD-۱ improved antigen-specific T-cell responses synergistically (P=۰.۰۱) when compared with respective monotherapy. Furthermore, when compared with the respective monotherapies, combination therapy significantly controlled tumor growth in B۱۰-F۱۶ tumor cells and increased survival rate.Conclusion: Treatments with anti-PD-۱ 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-۱ 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-۱ antibody antitumor response.

کلیدواژه ها:

Anti-PD-۱ ، antibody ، Antimicrobial peptides ، Cancer therapy ، Immunotherapy ، Melanoma cancer