Abstract 2915: Intratumoral co-injections of NK cells and neutralizing antibodies against the NKG2A inhibitory pathway achieve efficacious anti-tumor responses in a CD8 T cell and cDC1-dependent manner

Abstract

Abstract Local intratumoral NK cell activity is known to foster adaptive T cell-mediated immunity against cancer, that conceivably is inhibited by the interactions of the inhibitory receptor NKG2A with the MHC class I molecule HLA-E in humans or Qa-1b in mice. In this study, we found that intratumoral delivery of NK cells significantly attains therapeutic effects only if co-injected with anti-NKG2A and anti-Qa1b blocking monoclonal antibodies (mAb) in two solid mouse tumors models. Such therapeutic activity was contingent on endogenous CD8 T cells and on type-1 conventional dendritic cells (cDC1), which mediate cross-priming of tumor antigens. Moreover, the anti-tumor effects can be enhanced upon combination with anti-PD-1 mAb. This combination achieves at least partial abscopal efficacy against distant untreated tumors. In xenografted mice with HLA-E-expressing human cancer cells, intratumoral co-injection of allogeneic human NK cells and the clinical-grade anti-NKG2A mAb monalizumab synergistically achieved therapeutic effects and gave rise to stronger antibody-dependent cellular cytotoxicity (ADCC) in conjunction with cetuximab. In conclusion, these studies provide evidences for the therapeutic potential of on-site NK cell-based immunotherapies that may recruit endogenous T-cell responses. Citation Format: Maite Alvarez, Maria C. Ochoa, Carmen Molina, Alvaro Teijeira, Saray Garasa, Sandra Sanchez-Gregorio, Irene Olivera, Javier Glez-Vaz, Asunta Cirella, Gabriel Gomis, Jose Gonzalez-Gomariz, Pedro Berraondo, Ignacio Melero. Intratumoral co-injections of NK cells and neutralizing antibodies against the NKG2A inhibitory pathway achieve efficacious anti-tumor responses in a CD8 T cell and cDC1-dependent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2915.