{Reference Type}: Journal Article
{Title}: Intratumoral co-injection of NK cells and NKG2A-neutralizing monoclonal antibodies.
{Author}: Melero I;Ochoa MC;Molina C;Sanchez-Gregorio S;Garasa S;Luri-Rey C;Hervas-Stubbs S;Casares N;Elizalde E;Gomis G;Cirella A;Berraondo P;Teijeira A;Alvarez M;
{Journal}: EMBO Mol Med
{Volume}: 15
{Issue}: 11
{Year}: 2023 11 8
{Factor}: 14.26
{DOI}: 10.15252/emmm.202317804
{Abstract}: NK-cell reactivity against cancer is conceivably suppressed in the tumor microenvironment by the interaction of the inhibitory receptor NKG2A with the non-classical MHC-I molecules HLA-E in humans or Qa-1b in mice. We found that intratumoral delivery of NK cells attains significant therapeutic effects only if co-injected with anti-NKG2A and anti-Qa-1b blocking monoclonal antibodies against solid mouse tumor models. Such therapeutic activity was contingent on endogenous CD8 T cells and type-1 conventional dendritic cells (cDC1). Moreover, the anti-tumor effects were enhanced upon combination with systemic anti-PD-1 mAb treatment and achieved partial abscopal efficacy against distant non-injected tumors. In xenografted mice bearing HLA-E-expressing human cancer cells, intratumoral co-injection of activated allogeneic human NK cells and clinical-grade anti-NKG2A mAb (monalizumab) synergistically achieved therapeutic effects. In conclusion, these studies provide evidence for the clinical potential of intratumoral NK cell-based immunotherapies that exert their anti-tumor efficacy as a result of eliciting endogenous T-cell responses.