|Anti-NKG2A antibodies in anti-cancer immune therapy|
|NKG2A (expressed on T and NK cells) binds to HLA-E (expressed on host cells) to trigger immune suppressive signals of self-antigens presented by HLA-E, thus the interaction between NKG2A and HLA-E inhibits effector functions of T and NK cells. By the above mechanism, cancer cells also upregulate the expression of HLA-E on surface to evade immune surveillance, suggesting NKG2A blockage could be utilized as a therapeutic strategy to enhance anti-cancer immune responses. Andre and colleagues tested this hypothesis and published their data on Cell (here).
In the present study, authors demonstrated that Qa-1b (mouse homolog of HLA-E)-deficient tumour (A20 lymphoma model) showed a substantially slower growth rate compared to parental tumours. The tumour control observed in Qa-1b-deficient tumour required intact CD8 T and NK cells. Analyses of the tumour microenvironment demonstrated that tumour-infiltrating CD8 T cells and NK cells expressed certain levels of NKG2A and PD-1, suggesting the possible involvement of NKG2A in tumour immune evasion. Although administration of NKG2A antibodies did not improve survival of tumour-bearing mice, the combination of anti-NKG2A and anti-PD-L1 dramatically improved survival, where the abundance of effector memory T cells (CD44+CD62L-) in the spleen was increased. More relevantly to the clinical practice, NKG2A and HLA-E were observed to be expressed in human cancer. Consequently, authors develop a humanized NKG2A antibody, which was tested in the in vitro and in vivo of human patients. In the phase 2 trial authors conducted, the combination of anti-NKG2A and anti-EGFR antibodies were administered to patients with squamous cell carcinoma of head and neck that were previously treated with platinum-based chemotherapy. Eight out of 26 recruited patients showed partial response, and 14 patients showed stable disease, composing the disease control rate of 85%. Adverse events in the cohort were mild and not new to the known adverse events related to antibodies.
Although authors used different tumour models in animal studies and clinical trials in terms of both cancer types and therapeutic regimens, the importance of NKG2A antibodies in cancer immune therapy warrants further investigations.