Pseudocowpox virus, a novel vector to enhance the therapeutic efficacy of antitumor vaccination. Issue 5 (8th May 2022)

• Record Type: Journal Article
• Authors: Ramos, Rodrigo Nalio; Tosch, Caroline; Kotsias, Fiorella; Claudepierre, Marie‐Christine; Schmitt, Doris; Remy‐Ziller, Christelle; Hoffmann, Chantal; Ricordel, Marine; Nourtier, Virginie; Farine, Isabelle; Laruelle, Laurence; Hortelano, Julie; Spring‐Giusti, Clementine; Sedlik, Christine; Le Tourneau, Christophe; Hoffmann, Caroline; Silvestre, Nathalie; Erbs, Philippe; Bendjama, Kaidre; Thioudellet, Christine; Quemeneur, Eric; Piaggio, Eliane; Rittner, Karola
• Is Part Of: Clinical & translational immunology. Volume 11:Issue 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-08
• Subjects: adaptive immunity -- IFN‐α -- innate immunity -- intratumoral injection -- Poxviral cancer vaccine; Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1002/cti2.1392
• Languages: English
• ISSNs: 2050-0068

Abstract

Abstract: Objective: Antitumor viral vaccines, and more particularly poxviral vaccines, represent an active field for clinical development and translational research. To improve the efficacy and treatment outcome, new viral vectors are sought, with emphasis on their abilities to stimulate innate immunity, to display tumor antigens and to induce a specific T‐cell response. Methods: We screened for a new poxviral backbone with improved innate and adaptive immune stimulation using IFN‐α secretion levels in infected PBMC cultures as selection criteria. Assessment of virus effectiveness was made in vitro and in vivo . Results: The bovine pseudocowpox virus (PCPV) stood out among several poxviruses for its ability to induce significant secretion of IFN‐α. PCPV produced efficient activation of human monocytes and dendritic cells, degranulation of NK cells and reversed MDSC‐induced T‐cell suppression, without being offensive to activated T cells. A PCPV‐based vaccine, encoding the HPV16 E7 protein (PCPV‐E7), stimulated strong antigen‐specific T‐cell responses in TC1 tumor‐bearing mice. Complete regression of tumors was obtained in a CD8 + T‐cell‐dependent manner after intratumoral injection of PCPV‐E7, followed by intravenous injection of the cancer vaccine MVA‐E7. PCPV also proved active when injected repeatedly intratumorally in MC38 tumor‐bearing mice, generating tumor‐specific T‐cell responses without encoding a specific MC38 antigen. From a translational perspective, we demonstrated that PCPV‐E7 effectively stimulated IFN‐γ production by T cells from tumor‐draining lymph nodes of HPV + ‐infected cancer patients. Conclusion: We propose PCPV as a viral vector suitable for vaccination in the field of personalised cancer vaccines, in particular for heterologous prime‐boost regimens. Abstract : In this study, we identified an immunostimulatory vaccine vector, pseudocowpox virus (PCPV), selected on its capacity to induce type I IFN response in primary immune cells from healthy donors and cancer patients. PCPV reactivates the ex vivo T‐cell response of cancer patients. In murine tumor models, the use of the PCPV vaccine can lead to complete tumor regression and systemic immunity.