Insulin-like growth factor-binding protein-like 1 peptide–HLA-A*02:01 complex (IGFBPL1–HLA-A*02:01)

The Insulin-like growth factor-binding protein-like 1 (IGFBPL1) peptide–HLA-A*02:01 complex is a tumor-associated antigen primarily targeted in pediatric malignancies such as neuroblastoma and medulloblastoma [2, 7]. IGFBPL1 is an intracellular protein that acts as a dependency gene in these cancers, and its degradation products are presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01 [3, 10]. This peptide-MHC (pMHC) complex serves as a specific molecular signature that allows the immune system to identify tumor cells expressing the IGFBPL1 protein [2, 3]. Therapeutic interventions, most notably peptide-centric chimeric antigen receptor (PC-CAR) T cells, are designed to recognize this complex using TCR-like scFv binders [7, 10]. By targeting a non-mutated peptide derived from an essential oncoprotein, this approach aims to overcome the limitations of low mutational burdens in solid tumors [3, 7]. Clinical development focuses on patients who are HLA-A*02:01 positive and whose tumors show high IGFBPL1 expression [2, 7].

Other names

IGFBPL1 pMHCIGFBPL1-HLA-A2 complexIGFBPL1 peptide-MHC complexIGFBP-related protein 10 peptide-HLA-A*02:01IGFBP-rP4 peptide-HLA-A*02:01

TCR-like recognition of the peptide-MHC complex by chimeric antigen receptor (CAR) T cells, leading to T-cell activation and direct lysis of tumor cells.