Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth

Abstract

Ovarian cancer is the deadliest gynecological malignancy. Though most patients enter remission following initial interventions, relapse is common and often fatal. Accordingly, there is a substantial need for ovarian cancer therapies that prevent relapse. Following remission generated by surgical debulking and chemotherapy, but prior to relapse, resected and inactivated tumor tissue could be used as a personalized vaccine antigen source. The patient’s own tumor contains relevant antigens and, when combined with the appropriate adjuvant, could generate systemic antitumor immunity to prevent relapse. Here, we model this process in mice to investigate the optimal tumor preparation and vaccine adjuvant. Cowpea mosaic virus (CPMV) has shown remarkable efficacy as an immunostimulatory cancer therapy in ovarian cancer mouse models, so we use CPMV as an adjuvant in a prophylactic vaccine against a murine ovarian cancer model. Compared to its codelivery with tumor antigens prepared in three other ways, we show that CPMV co-delivered with irradiated ovarian cancer cells constitutes an effective prophylactic vaccine against a syngeneic model of ovarian cancer in C57BL/6J mice. Following two vaccinations, 72% of vaccinated mice reject tumor challenges, and all those mice survived subsequent rechallenges, demonstrating immunologic memory formation. This study supports remission-stage vaccines using irradiated patient tumor tissue as a promising option for treating ovarian cancer, and validates CPMV as an antitumor vaccine adjuvant for that purpose.

Inactivated Cowpea Mosaic Virus for In Situ Vaccination: Differential Efficacy of Formalin vs UV-Inactivated Formulations

“…CPMV has unique potency and it outperforms classical adjuvants as well as other plant viruses . CPMV is more potent compared to small-molecule TLR or STING agonists. , This can be explained by the nanoparticle character enabling prolonged tumor retention and multivalent and multipronged engagement of TLR receptors. , Hence, CPMV offers advantages compared to synthetic small-molecule therapeutics because it mimics a viral pathogen or danger signal more closely. Additional advantages are conferred over mammalian oncolytic therapies: production through plant molecular farming is highly scalable and high yielding; 1 mg of CPMV can be obtained per 1 g of infected leaf tissue.…”

Cowpea Mosaic Virus Outperforms Other Members of the Secoviridae as In Situ Vaccine for Cancer Immunotherapy

“…22,24 We have demonstrated efficacy of CPMV as solo-treatment and in combination with radiation, 25 chemotherapy, 26 and checkpoint inhibitors. 27 Importantly, we found that CPMV has unique potency when used as ISV, that is, used as immunostimulatory agent administered directly into a tumor, compared to other nonrelated plant viruses, bacteriophage VLPs or mammalian VLPs, 28 or small molecule adjuvants 17,29 in terms of immune activation mechanisms and antitumor efficacy. Specifically, we compared efficacy and mechanism of immune activation of CPMV versus tobacco mosaic virus, 16 potato virus X, 30 cowpea chlorotic mottle virus, physalis mosaic virus-like particles, sesbania mosaic virus, Qβ phage VLPs, and Hepatitis B core particles 28 and data show while all virus-based nanoparticles are immunogenic, only CPMV-ISV primes potent antitumor immunity.…”

Nanomedicine Strategies for Heating “Cold” Ovarian Cancer (OC): Next Evolution in Immunotherapy of OC

“…Additionally, VLPs can also be adopted in combination with ICIs to increase the therapeutic effect of immunotherapy. [90,91] For example, Gautam et al covalently linked the PD-1 antibody peptide (SNTSESF) to CPMV for OC immunotherapy. [92] SNTSESF, also known as AUR-7, is a potent ICI mimicking the endogenous PD-1 receptor to inhibit PD-1 function.…”

“…Additionally, VLPs can also be adopted in combination with ICIs to increase the therapeutic effect of immunotherapy. [ 90 , 91 ] For example, Gautam et al. covalently linked the PD‐1 antibody peptide (SNTSESF) to CPMV for OC immunotherapy.…”