Intratumoral co-injection of NK cells and NKG2A-neutralizing monoclonal antibodies. Scientific Publication

Oct 2, 2023 | Magazine: EMBO Molecular Medicine

Ignacio Melero 1 2 3 4 , Maria C Ochoa 1 2 3 , Carmen Molina 1 2 , Sandra Sanchez-Gregorio 1 2 , Saray Garasa 1 2 , Carlos Luri-Rey 1 2 , Sandra Hervas-Stubbs 1 2 , Noelia Casares 1 2 , Edurne Elizalde 1 2 , Gabriel Gomis 1 2 , Assunta Cirella 1 2 , Pedro Berraondo 1 2 3 , Alvaro Teijeira 1 2 3 , Maite Alvarez 1 2 3 5 6

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.

CITATION EMBO Mol Med. 2023 Oct 2:e17804. doi: 10.15252/emmm.202317804

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