Immunoglobulin lambda variable 3-21 R110-mutated B-cell receptor light chain neoepitope (IGLV3-21 R110)

The Immunoglobulin lambda variable 3-21 R110-mutated B-cell receptor light chain neoepitope is a tumor-specific antigen primarily associated with an aggressive subset of Chronic Lymphocytic Leukemia (CLL). This neoepitope is characterized by the presence of an arginine residue at position 110 (R110) of the IGLV3-21 light chain, which typically results from a specific V-J rearrangement involving the IGLJ3 joining segment (Minici et al., 2017, Nature Communications). Biologically, this mutation is significant because it enables homotypic interactions between B-cell receptors (BCRs), leading to autonomous, ligand-independent signaling that promotes the survival and proliferation of malignant B cells (Nadeu et al., 2021, Blood). Because the R110 mutation is absent in the germline and healthy B cells, it represents an ideal neoantigen for precision immunotherapy. Current therapeutic strategies under investigation include chimeric antigen receptor (CAR) T-cells and bispecific antibodies designed to recognize the unique structural motif created by the R110 residue (Maity et al., 2022, Cancer Discovery). Targeting this neoepitope offers a potential pathway to treat high-risk CLL patients who exhibit poor responses to conventional therapies and BTK inhibitors.

Other names

IGLV3-21*01 R110IGLV3-21-mutated B-cell receptorR110-mutated lambda light chainCLL-specific IGLV3-21 neoantigen

Targeted T-cell mediated cytotoxicity against cells expressing the R110-mutated B-cell receptor