We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely.

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV / Gianni T.; Leoni V.; Sanapo M.; Parenti F.; Bressanin D.; Barboni C.; Zaghini A.; Campadelli-Fiume G.; Vannini A.. - In: VIRUSES. - ISSN 1999-4915. - ELETTRONICO. - 13:9(2021), pp. 1747.1-1747.18. [10.3390/v13091747]

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

Gianni T.
Investigation
;
Leoni V.
Investigation
;
Sanapo M.
Membro del Collaboration Group
;
Parenti F.
Membro del Collaboration Group
;
Bressanin D.
Investigation
;
Barboni C.
Membro del Collaboration Group
;
Zaghini A.
Membro del Collaboration Group
;
Campadelli-Fiume G.
Supervision
;
Vannini A.
Validation
2021

Abstract

We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely.
2021
Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV / Gianni T.; Leoni V.; Sanapo M.; Parenti F.; Bressanin D.; Barboni C.; Zaghini A.; Campadelli-Fiume G.; Vannini A.. - In: VIRUSES. - ISSN 1999-4915. - ELETTRONICO. - 13:9(2021), pp. 1747.1-1747.18. [10.3390/v13091747]
Gianni T.; Leoni V.; Sanapo M.; Parenti F.; Bressanin D.; Barboni C.; Zaghini A.; Campadelli-Fiume G.; Vannini A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/858049
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