Prostate specific membrane antigen (PSMA) is a specific high frequency cell surface marker of prostate cancers. Theranostic approaches targeting PSMA show no major adverse effects and rule out off-tumor toxicity. A PSMA-retargeted oHSV (R-405) was generated which both infected and was cytotoxic exclusively for PSMA-positive cells, including human prostate cancer LNCaP and 22Rv1 cells, and spared PSMA-negative cells. R-405 in vivo efficacy against LLC1PSMA and Renca-PSMA tumors consisted of inhibiting primary tumor growth, establishing longterm T immune response, immune heating of the microenvironment, de-repression of the antitumor immune phenotype, and sensitization to checkpoint blockade. The in situ vaccination protected from distant challenge tumors, both PSMA-positive and PSMA-negative, implying that it was addressed also to LLC1 tumor antigens. PSMA-retargeted oHSVs are a precision medicine tool worth being additionally investigated in the immunotherapeutic and in situ vaccination landscape against prostate cancers.
Towards a precision medicine approach and in situ vaccination against prostate cancer by psma-retargeted ohsv / Vannini A.; Parenti F.; Bressanin D.; Barboni C.; Zaghini A.; Campadelli-Fiume G.; Gianni T.. - In: VIRUSES. - ISSN 1999-4915. - ELETTRONICO. - 13:10(2021), pp. 2085.1-2085.22. [10.3390/v13102085]
Towards a precision medicine approach and in situ vaccination against prostate cancer by psma-retargeted ohsv
Vannini A.;Parenti F.;Bressanin D.;Barboni C.;Zaghini A.;Campadelli-Fiume G.
;Gianni T.
2021
Abstract
Prostate specific membrane antigen (PSMA) is a specific high frequency cell surface marker of prostate cancers. Theranostic approaches targeting PSMA show no major adverse effects and rule out off-tumor toxicity. A PSMA-retargeted oHSV (R-405) was generated which both infected and was cytotoxic exclusively for PSMA-positive cells, including human prostate cancer LNCaP and 22Rv1 cells, and spared PSMA-negative cells. R-405 in vivo efficacy against LLC1PSMA and Renca-PSMA tumors consisted of inhibiting primary tumor growth, establishing longterm T immune response, immune heating of the microenvironment, de-repression of the antitumor immune phenotype, and sensitization to checkpoint blockade. The in situ vaccination protected from distant challenge tumors, both PSMA-positive and PSMA-negative, implying that it was addressed also to LLC1 tumor antigens. PSMA-retargeted oHSVs are a precision medicine tool worth being additionally investigated in the immunotherapeutic and in situ vaccination landscape against prostate cancers.File | Dimensione | Formato | |
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