Towards a Precision Medicine Approach and In Situ Vaccination against Prostate Cancer by PSMA-Retargeted oHSV |
| |
| Authors: | Andrea Vannini Federico Parenti Daniela Bressanin Catia Barboni Anna Zaghini Gabriella Campadelli-Fiume Tatiana Gianni |
| |
| Affiliation: | 1.Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy; (A.V.); (F.P.); (D.B.);2.Department of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, Italy; (C.B.); (A.Z.) |
| |
| 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 LLC1-PSMA and Renca-PSMA tumors consisted of inhibiting primary tumor growth, establishing long-term T immune response, immune heating of the microenvironment, de-repression of the anti-tumor 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. |
| |
| Keywords: | oncolytic virus oncolytic herpes simplex virus retargeting PSMA prostate cancer vaccination in situ vaccine immunotherapy immune checkpoint inhibitors |
|
|
