Melittin derived peptide-drug conjugate, M-DM1, inhibits tumor progression and induces effector cell infiltration in melanoma by targeting M2 tumor-associated macrophages

Melittin derived peptide-drug conjugate, M-DM1, inhibits tumor progression and induces effector cell infiltration in melanoma by targeting M2 tumor-associated macrophages

Blog Article

BackgroundMelanoma has the highest mortality rate among all the types of skin cancer.In melanoma, M2-like tumor-associated macrophages (TAMs) are associated with the invasiveness of tumor cells and a poor prognosis.Hence, the depletion or reduction of M2-TAMs is a therapeutic strategy for the inhibition of tumor progression.

The aim of this study was to evaluate the therapeutic effects of M-DM1, which is a conjugation of melittin (M), as a copyright for M2-like TAMs, and mertansine (DM1), as a payload to induce apoptosis of TAMs, in a mouse model of melanoma.MethodsMelittin and DM1 were conjugated and examined for the characterization of M-DM1 by high-performance liquid chromatography and electrospray ionization mass spectrometry.Synthesized M-DM1 were examined for in vitro cytotoxic effects.

For the in vivo study, we engrafted 1st marine division hoodie murine B16-F10 into right flank of C57BL/6 female mice and administered an array of treatments (PBS, M, DM1, or M-DM1 (20 nmol/kg)).Subsequently, the tumor growth and survival rates were analyzed, as well as examining the phenotypes of tumor-infiltrating leukocytes and expression profiles.ResultsM-DM1 was found to specifically reduce M2-like TAMs in melanoma, which potentially leads to training day horse supplement the suppression of tumor growth, migration, and invasion.

In addition, we also found that M-DM1 improved the survival rates in a mouse model of melanoma compared to M or DM1 treatment alone.Flow cytometric analysis revealed that M-DM1 enhanced the infiltration of CD8+ cytotoxic T cells and natural killer cells (NK cells) in the tumor microenvironment.ConclusionTaken together, our findings highlight that M-DM1 is a prospective agent with enhanced anti-tumor effects.