Methyl-lysophosphatidic acid (mLPA)

Methyl-lysophosphatidic acid (mLPA) is a tumor-associated lipid antigen that has emerged as a novel therapeutic target for the treatment of hematological malignancies, including acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL). It is a unique phospholipid derivative characterized by a methyl group on the phosphate headgroup and an ether-linked alkyl chain, synthesized through altered metabolic pathways in malignant cells (Lepore et al., 2014). Unlike conventional peptide antigens presented by MHC molecules, mLPA is presented by the non-polymorphic CD1c protein, which is highly expressed on the surface of various leukemia cells (Lepore et al., 2015). This presentation allows for the activation of specialized T cells that recognize the mLPA-CD1c complex, triggering a potent cytotoxic immune response against the tumor. Because mLPA is significantly upregulated in leukemic blasts compared to normal hematopoietic cells, it offers a high degree of tumor selectivity for immunotherapy. Current research is focused on developing mLPA-specific T-cell receptors (TCRs) for use in adoptive T-cell therapies and TCR-engineered T-cell treatments.

Other names

mLPAMethyl-LPA1-O-hexadecyl-sn-glycero-3-phosphoric acid methyl esterC16-methyl-lysophosphatidic acidC18-methyl-lysophosphatidic acid

Presentation by CD1c molecules on the surface of leukemia cells, which is then recognized by specific T-cell receptors (TCRs), leading to T-cell activation and targeted cytotoxicity against the tumor cells.