ABX002 TCR-mimic antibody dissects HLA-E biology, restores cytotoxic function by disrupting NKG2A checkpoint.

The human leukocyte antigen E (HLA-E) molecule functions as a crucial immune checkpoint in cancer immunity, influencing the activity of natural killer (NK) cells and T cells. Its checkpoint activity is contingent on the display of a specific canonical peptide, VL9. However, direct and precise profiling of these VL9/HLA-E complexes in situ has been severely hampered by the absence of highly specific and sensitive reagents. This lack of tools has created a significant gap in our understanding of HLA-E biology and its role in immune evasion within the tumor microenvironment.

Researchers developed ABX002, a novel fully human TCR-mimic antibody, engineered to specifically recognize all tested VL9/HLA-E complexes with high affinity and specificity in situ. They utilized ABX002 to conduct cell-type and context-specific quantification of HLA-E antigen presentation across various cell types and tumor samples. Furthermore, the team employed ABX002 to investigate its functional impact on the NKG2A immune checkpoint, assessing its ability to restore cytotoxic lymphocyte function in relevant in vitro models.

ABX002 demonstrated high affinity and specificity for all tested VL9/HLA-E complexes, enabling unprecedented insight into HLA-E biology. The antibody revealed that canonical VL9/HLA-E surface expression is tightly controlled by inflammatory cues. Notably, VL9/HLA-E expression was found to be remarkably infrequent on tumors without stimulation. Moreover, expression was almost absent from immune cells, with the exception of myeloid-lineage cells. This precise mapping provides critical context for HLA-E's role in immune evasion. > ABX002 additionally disrupts the NKG2A checkpoint, successfully restoring cytotoxic lymphocyte function, thereby offering a direct mechanism for overcoming HLA-E-mediated immunosuppression. These findings collectively position ABX002 as a transformative tool for dissecting the landscape and biology of canonical peptide restriction in cancer immunity.