Immunotherapy enhancement with MACTIDE-V peptide-drug conjugate for cancer treatment

Overview

MACTIDE-V is a groundbreaking peptide-drug conjugate that targets tumor-associated macrophages (TAMs) to reprogram them into an antitumoral phenotype, particularly in metastatic triple negative breast cancer (mTNBC). Developed by CSIC, this orally-available conjugate aims to enhance the immunostimulatory capacity of macrophages, increasing tumor-infiltrating NK and cytotoxic T-cells while reducing regulatory T-cells. Although it effectively suppresses pulmonary metastases, its synergy with other TAM-targeting therapies holds promise for further improving cancer treatment outcomes.

Technical specifications

MACTIDE-V consists of the macrophage-targeting peptide MACTIDE linked to Verteporfin, a therapeutic agent. This conjugate has demonstrated increased phagocytosis activity in macrophages, both in vitro and in vivo, and induces the expression of phagocytosis markers. The ongoing research seeks to combine MACTIDE-V with agents targeting macrophage "don't eat me" signals such as ligands of Siglecs, Sirpa, and CD300a/f. Future experiments will evaluate these combinations to enhance immunostimulatory cytokine production.

Technology readiness level

The current development stage of MACTIDE-V is at Technology Readiness Level 4. This level indicates successful validation of the technology in laboratory settings. The next steps involve further in vitro and in vivo testing to optimize drug combinations and assess therapeutic effects in animal models, with future studies planned for melanoma and colorectal cancer.