B-cell lymphoma-extra large (Bcl-XL)-derived peptide epitopes presented on Major Histocompatibility Complex (MHC) (Bcl-XL/MHC)

B-cell lymphoma-extra large (Bcl-XL), encoded by the BCL2L1 gene, is a potent anti-apoptotic protein that promotes cell survival by inhibiting the mitochondrial pathway of programmed cell death (Andersen et al., 2005, Cancer Res). In many malignancies, Bcl-XL is overexpressed, which facilitates tumor cell evasion from apoptosis and confers resistance to conventional therapies (Letai, 2015, Nat Rev Cancer). Peptide epitopes derived from the degradation of Bcl-XL are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, primarily MHC Class I, where they can be recognized by the T-cell receptors (TCRs) of cytotoxic T-lymphocytes (Andersen et al., 2005). These Bcl-XL/MHC complexes represent a significant therapeutic target for cancer vaccines and TCR-engineered T-cell therapies designed to induce a specific immune response against tumor cells (IO Biotech, 2024). For instance, the therapeutic vaccine IO-102/IO-103 targets Bcl-XL and IDO1 to activate T cells against both the tumor cells and the immunosuppressive cells in the microenvironment (ClinicalTrials.gov, NCT05155254). While promising, targeting these epitopes requires careful management of potential off-tumor effects, as Bcl-XL is also expressed in healthy tissues such as platelets and certain neurons (Mason et al., 2007, Cell).

Other names

Bcl-XL peptide-HLA complexBCL2L1-derived epitopesBcl-XL T-cell epitopesBcl-XL/MHC class I complex

Induction of T-cell mediated cytotoxicity against cells presenting Bcl-XL-derived peptides on MHC molecules, typically through therapeutic vaccination or TCR-based recognition.