2. Academic Validation
  3. Intratumoral co-injection of NK cells and NKG2A-neutralizing monoclonal antibodies

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

  • EMBO Mol Med. 2023 Nov 8;15(11):e17804. doi: 10.15252/emmm.202317804.
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
Affiliations

Affiliations

  • 1 Program for Immunology and Immunotherapy, CIMA, Universidad de Navarra, Pamplona, Spain.
  • 2 Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
  • 3 Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • 4 Departments of Immunology and Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
  • 5 Cell Therapy, Stem Cells and Tissue Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
  • 6 Research Unit, Basque Center for Blood Transfusion and Human Tissues, Osakidetza, Galdakao, Spain.
PMID: 37782273 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.

Keywords

HLA-E; NK; NKG2A; Qa-1b; intratumoral immunotherapy.

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