Alpha-lactalbumin peptide-MHC complex (α-LA pMHC)

Alpha-lactalbumin is a mammary-specific protein that is normally expressed only during lactation, making it a "retired" protein in non-lactating women (Tuohy et al., 2010, Nature Medicine). However, it is frequently overexpressed in triple-negative breast cancer (TNBC), where it serves as a tumor-associated antigen (Jain et al., 2022, Frontiers in Oncology). The therapeutic target is the specific peptide fragment of alpha-lactalbumin presented by Major Histocompatibility Complex (MHC) molecules on the surface of cancer cells. This peptide-MHC (pMHC) complex is recognized by T-cell receptors (TCRs), which triggers a cytotoxic immune response against the tumor. Current clinical efforts, such as the CVI-VB-001 vaccine developed by the Cleveland Clinic and Anixa Biosciences, aim to stimulate the immune system to recognize this complex (ClinicalTrials.gov, NCT04645004). Because alpha-lactalbumin is not found in other healthy tissues, targeting this pMHC complex minimizes off-target toxicity. The primary safety concern is the potential for autoimmune mastitis, which is only relevant to women who are currently lactating or intend to breastfeed. This target represents a significant opportunity for precision immunotherapy in aggressive breast cancer subtypes that lack traditional receptors like HER2 or estrogen receptors.

Other names

α-lactalbumin-derived peptide-MHCLALBA peptide-HLA complexAlpha-lactalbumin epitopeα-LA-MHC complexα-lactalbumin-derived peptide presented on MHC

Vaccine-induced or adoptive T-cell recognition of the alpha-lactalbumin peptide-MHC complex, leading to targeted lysis of tumor cells expressing the antigen.