MM185

MM185 is a novel peptide-drug conjugate (PDC) designed for the treatment of chronic myelomonocytic leukaemia (CMML). It consists of a recombinant human CCL2 (C-C motif chemokine ligand 2) peptide conjugated to a broad-acting, cell-cycle independent cytotoxic payload using transglutaminase (TGase)-mediated site-specific conjugation. MM185 selectively targets the C-C chemokine receptor type 2 (CCR2), which is highly expressed on disease-propagating CD14+ monocytes and disease-initiating CD34+ stem cells in CMML patients. Upon binding to CCR2 and subsequent internalization, the conjugate releases its cytotoxic payload, inducing DNA damage (marked by gH2AX induction) and triggering apoptosis through the activation of caspases 3 and 9 and the cleavage of PARP-1. Preclinical studies have demonstrated that MM185 effectively reduces the viability of CCR2-expressing leukemia cell lines and primary CMML samples while sparing CCR2-negative cells. In vivo xenograft models have shown that MM185 treatment leads to a significant reduction in leukemic cell engraftment in the bone marrow, spleen, and liver, resulting in improved survival.

Other names

CCL2-drug conjugateCCL-2-drug conjugateCCL 2-drug conjugate