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Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

ABSTRACT: Oncolytic viral therapy is an emerging new class of immunotherapy that involves selectively infecting and killing tumor cells. Several oncolytic viruses (OVs) have exhibited promising potential for treating human cancer in animal models and clinical trials, including hepatocellular carcinoma (HCC). However, despite clinical evidence and benefit for patients, the cost-intensive manufacturing and testing nature of oncolytic viral products makes them far out of reach for most US patients. We propose to develop a cost-effective immunovirotherapy approach that could synergize with other therapies to improve the outcomes for patients with advanced HCC. Specifically, we showed that intratumoral administration of low doses of the live attenuated measles, mumps and rueball viruses (MMR) vaccine effectively activates a robust cytotoxic T cells response, leading to tumor regression and extended survival in the syngeneic HCC model. Using transcriptomic approach, we showed that mechanistically MMR exerts its anti-tumor activity by priming innate and adaptive anti-tumor immune responses, leading to immunologically coordinated death of cancer cells. The proposed research can impact cancer patients globally, and our multidisciplinary team is uniquely equipped to execute the proposed studies.

ORGANISM(S): Mus musculus

PROVIDER: GSE199131 | GEO | 2025/01/08

REPOSITORIES: GEO

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Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer ImmunotherapyRepurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

Project description:In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulate a potent cytotoxic T cells immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma (HCC) and colorectal cancer (CRC).

2022-10-27 | PXD031295 | Pride

Reshaping of the MHC-I ligandome in response to reovirus-based cancer immunotherapy

Project description:Oncolytic viruses (OVs), known for their cancer-killing characteristics, overturn tumor-associated defects in antigen presentation through the MHC class I pathway and induce protective neo antitumor CD8 T cell responses. Nonetheless, whether OVs shape the tumor MHC-I ligandome remains unknown. Here, we investigated if an OV induces the presentation of novel MHC I-bound tumor antigens (termed tumor MHC-I ligands). Using comparative mass spectrometry (MS)-based MHC-I ligandomics, we determined differential tumor MHC-I ligand expression following treatment with oncolytic reovirus in a murine ovarian cancer model. In vitro we found that reovirus induces the presentation of tumor MHC-I ligands in cancer cells. Concurrent multiplexed quantitative proteomics revealed that the changes in tumor MHC-I ligand presentation were mostly independent of reovirus-induced alterations of their source proteins. In an in vivo model, tumor MHC-I ligands were induced by reovirus in tumors but also, more importantly, analysis of spleens (a source of antigen-presenting cells) showed exclusive induction of most MHC-I ligands occurred in tumor-bearing mice. Finally, IFNγ assays demonstrated immunogenicity of the reovirus-induced MHC-I ligands. OV-induced MHC-I responses may be exploited in combinatorial approaches to promote the efficacy of cancer immunotherapies.

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The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene molecular profiles

Project description:Despite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal, however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). Therefore, we employ four different species of OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124 and the non-virulent Newcastle Disease Virus rNDV-F0-GFP against three entities of PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors and ependymomas) to determine their in vitro efficacy. These four OVs were screened on 14 patient-derived spheroids and the degree of oncolysis was assessed using an ATP-based assay. Subsequently, the observed viral efficacies were correlated to whole transcriptome data and Gene Ontology analysis was performed. Although no significant tumor type-specific OV efficacy was observed, whole transcriptome analysis revealed the intrinsic biological processes that associated with OV efficacy. The predictive power of those molecular profiles was further validated by screening the OV in vitro efficacy on additional PBTs. In summary, our results demonstrate OV susceptibility of multiple patient-derived PBT entities and the ability to predict in vitro responses to OVs using unique molecular profiles. Those profiles highlight the cellular intrinsic factors for potent oncolysis, that could potentially allow stratification of patients and lead to improved OV responses.

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Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens

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The clinicopathological characteristics, prognosis and immune microenvironment mapping in MSI-H/MMR-D endometrial carcinomas

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MMR in mCRPC

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| PRJEB27287 | ENA

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