Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) (IGF2BP3)

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), widely known in oncology as the L523S oncofetal antigen, is a member of the VICKZ family of RNA-binding proteins (UniProt: Q9UBU8). It is highly expressed during fetal development but is virtually undetectable in normal adult tissues, whereas it is significantly overexpressed in various malignancies, particularly non-small cell lung cancer (NSCLC) (PubMed: 11502514). In the context of cancer, L523S functions by binding to and stabilizing oncogenic mRNAs, such as IGF2 and CD44, thereby promoting tumor cell proliferation, survival, and metastasis (PubMed: 24633448). Peptides derived from the L523S protein are processed intracellularly and presented on the cell surface in complex with Major Histocompatibility Complex (MHC) Class I molecules, most notably HLA-A*02:01 (PubMed: 12844495). This specific peptide-MHC presentation makes L523S an ideal target for immunotherapies, including cancer vaccines and T-cell receptor (TCR)-engineered T-cell therapies, which aim to direct the immune system to selectively destroy cells expressing the antigen. Clinical and preclinical efforts have focused on leveraging this target to provide a highly specific treatment for NSCLC patients while minimizing damage to healthy tissues (PubMed: 12844495).

Other names

L523SIMP3KOCVICKZ3KH domain-containing protein overexpressed in cancerInsulin-like growth factor 2 mRNA-binding protein 3

Induction of a cytotoxic T-lymphocyte (CTL) response through the recognition of L523S-derived peptides presented on MHC Class I molecules, leading to the targeted lysis of cancer cells.