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mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy

Interleukin-12 (IL-12) gene transfer enhances the therapeutic potency of adoptive T cell therapies. We previously reported that transient engineering of tumor-specific CD8 T cells with IL-12 mRNA enhanced their systemic therapeutic efficacy when delivered intratumorally. Here, we mix T cells enginee...

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Autores principales: Olivera, Irene, Bolaños, Elixabet, Gonzalez-Gomariz, Jose, Hervas-Stubbs, Sandra, Mariño, Karina V., Luri-Rey, Carlos, Etxeberria, Iñaki, Cirella, Assunta, Egea, Josune, Glez-Vaz, Javier, Garasa, Saray, Alvarez, Maite, Eguren-Santamaria, Iñaki, Guedan, Sonia, Sanmamed, Miguel F., Berraondo, Pedro, Rabinovich, Gabriel A., Teijeira, Alvaro, Melero, Ignacio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040457/
https://www.ncbi.nlm.nih.gov/pubmed/36933554
http://dx.doi.org/10.1016/j.xcrm.2023.100978
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author Olivera, Irene
Bolaños, Elixabet
Gonzalez-Gomariz, Jose
Hervas-Stubbs, Sandra
Mariño, Karina V.
Luri-Rey, Carlos
Etxeberria, Iñaki
Cirella, Assunta
Egea, Josune
Glez-Vaz, Javier
Garasa, Saray
Alvarez, Maite
Eguren-Santamaria, Iñaki
Guedan, Sonia
Sanmamed, Miguel F.
Berraondo, Pedro
Rabinovich, Gabriel A.
Teijeira, Alvaro
Melero, Ignacio
author_facet Olivera, Irene
Bolaños, Elixabet
Gonzalez-Gomariz, Jose
Hervas-Stubbs, Sandra
Mariño, Karina V.
Luri-Rey, Carlos
Etxeberria, Iñaki
Cirella, Assunta
Egea, Josune
Glez-Vaz, Javier
Garasa, Saray
Alvarez, Maite
Eguren-Santamaria, Iñaki
Guedan, Sonia
Sanmamed, Miguel F.
Berraondo, Pedro
Rabinovich, Gabriel A.
Teijeira, Alvaro
Melero, Ignacio
author_sort Olivera, Irene
collection PubMed
description Interleukin-12 (IL-12) gene transfer enhances the therapeutic potency of adoptive T cell therapies. We previously reported that transient engineering of tumor-specific CD8 T cells with IL-12 mRNA enhanced their systemic therapeutic efficacy when delivered intratumorally. Here, we mix T cells engineered with mRNAs to express either single-chain IL-12 (scIL-12) or an IL-18 decoy-resistant variant (DRIL18) that is not functionally hampered by IL-18 binding protein (IL-18BP). These mRNA-engineered T cell mixtures are repeatedly injected into mouse tumors. Pmel-1 T cell receptor (TCR)-transgenic T cells electroporated with scIL-12 or DRIL18 mRNAs exert powerful therapeutic effects in local and distant melanoma lesions. These effects are associated with T cell metabolic fitness, enhanced miR-155 control on immunosuppressive target genes, enhanced expression of various cytokines, and changes in the glycosylation profile of surface proteins, enabling adhesiveness to E-selectin. Efficacy of this intratumoral immunotherapeutic strategy is recapitulated in cultures of tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells on IL-12 and DRIL18 mRNA electroporation.
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spelling pubmed-100404572023-03-28 mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy Olivera, Irene Bolaños, Elixabet Gonzalez-Gomariz, Jose Hervas-Stubbs, Sandra Mariño, Karina V. Luri-Rey, Carlos Etxeberria, Iñaki Cirella, Assunta Egea, Josune Glez-Vaz, Javier Garasa, Saray Alvarez, Maite Eguren-Santamaria, Iñaki Guedan, Sonia Sanmamed, Miguel F. Berraondo, Pedro Rabinovich, Gabriel A. Teijeira, Alvaro Melero, Ignacio Cell Rep Med Article Interleukin-12 (IL-12) gene transfer enhances the therapeutic potency of adoptive T cell therapies. We previously reported that transient engineering of tumor-specific CD8 T cells with IL-12 mRNA enhanced their systemic therapeutic efficacy when delivered intratumorally. Here, we mix T cells engineered with mRNAs to express either single-chain IL-12 (scIL-12) or an IL-18 decoy-resistant variant (DRIL18) that is not functionally hampered by IL-18 binding protein (IL-18BP). These mRNA-engineered T cell mixtures are repeatedly injected into mouse tumors. Pmel-1 T cell receptor (TCR)-transgenic T cells electroporated with scIL-12 or DRIL18 mRNAs exert powerful therapeutic effects in local and distant melanoma lesions. These effects are associated with T cell metabolic fitness, enhanced miR-155 control on immunosuppressive target genes, enhanced expression of various cytokines, and changes in the glycosylation profile of surface proteins, enabling adhesiveness to E-selectin. Efficacy of this intratumoral immunotherapeutic strategy is recapitulated in cultures of tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells on IL-12 and DRIL18 mRNA electroporation. Elsevier 2023-03-17 /pmc/articles/PMC10040457/ /pubmed/36933554 http://dx.doi.org/10.1016/j.xcrm.2023.100978 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Olivera, Irene
Bolaños, Elixabet
Gonzalez-Gomariz, Jose
Hervas-Stubbs, Sandra
Mariño, Karina V.
Luri-Rey, Carlos
Etxeberria, Iñaki
Cirella, Assunta
Egea, Josune
Glez-Vaz, Javier
Garasa, Saray
Alvarez, Maite
Eguren-Santamaria, Iñaki
Guedan, Sonia
Sanmamed, Miguel F.
Berraondo, Pedro
Rabinovich, Gabriel A.
Teijeira, Alvaro
Melero, Ignacio
mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
title mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
title_full mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
title_fullStr mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
title_full_unstemmed mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
title_short mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy
title_sort mrnas encoding il-12 and a decoy-resistant variant of il-18 synergize to engineer t cells for efficacious intratumoral adoptive immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040457/
https://www.ncbi.nlm.nih.gov/pubmed/36933554
http://dx.doi.org/10.1016/j.xcrm.2023.100978
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