Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies
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 therapeu...
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Springer Nature
2023-10-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202317804 |
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| author | Ignacio Melero Maria C Ochoa Carmen Molina Sandra Sanchez‐Gregorio Saray Garasa Carlos Luri‐Rey Sandra Hervas‐Stubbs Noelia Casares Edurne Elizalde Gabriel Gomis Assunta Cirella Pedro Berraondo Alvaro Teijeira Maite Alvarez |
| author_facet | Ignacio Melero Maria C Ochoa Carmen Molina Sandra Sanchez‐Gregorio Saray Garasa Carlos Luri‐Rey Sandra Hervas‐Stubbs Noelia Casares Edurne Elizalde Gabriel Gomis Assunta Cirella Pedro Berraondo Alvaro Teijeira Maite Alvarez |
| author_sort | Ignacio Melero |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dad7d8e3e32044ab82bb7ccfc15b4a39 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-dad7d8e3e32044ab82bb7ccfc15b4a392025-08-20T04:02:55ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-10-01151111610.15252/emmm.202317804Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodiesIgnacio Melero0Maria C Ochoa1Carmen Molina2Sandra Sanchez‐Gregorio3Saray Garasa4Carlos Luri‐Rey5Sandra Hervas‐Stubbs6Noelia Casares7Edurne Elizalde8Gabriel Gomis9Assunta Cirella10Pedro Berraondo11Alvaro Teijeira12Maite Alvarez13Program for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraProgram for Immunology and Immunotherapy, CIMA, Universidad de NavarraAbstract 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.https://doi.org/10.15252/emmm.202317804HLA‐Eintratumoral immunotherapyNKNKG2AQa‐1b |
| spellingShingle | Ignacio Melero Maria C Ochoa Carmen Molina Sandra Sanchez‐Gregorio Saray Garasa Carlos Luri‐Rey Sandra Hervas‐Stubbs Noelia Casares Edurne Elizalde Gabriel Gomis Assunta Cirella Pedro Berraondo Alvaro Teijeira Maite Alvarez Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies EMBO Molecular Medicine HLA‐E intratumoral immunotherapy NK NKG2A Qa‐1b |
| title | Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies |
| title_full | Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies |
| title_fullStr | Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies |
| title_full_unstemmed | Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies |
| title_short | Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies |
| title_sort | intratumoral co injection of nk cells and nkg2a neutralizing monoclonal antibodies |
| topic | HLA‐E intratumoral immunotherapy NK NKG2A Qa‐1b |
| url | https://doi.org/10.15252/emmm.202317804 |
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