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

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

PROVIDER: PRJNA818636 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18431661_1.fastq.gz	Fastqsanger.gz
	SRR18431661_2.fastq.gz	Fastqsanger.gz
	SRR18431662_1.fastq.gz	Fastqsanger.gz
	SRR18431662_2.fastq.gz	Fastqsanger.gz
	SRR18431663_1.fastq.gz	Fastqsanger.gz

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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

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

Project description: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.

2025-01-08 | GSE199131 | GEO

Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy.

Project description:It has long been known that oncolytic viruses wield their therapeutic capability by priming an inflammatory state within the tumor and activating the tumor immune microenvironment, resulting in a multifaceted antitumor immune response. Vaccine-derived viruses, such as measles and mumps, have demonstrated promising potential for treating human cancer in animal models and clinical trials. However, the extensive cost of manufacturing current oncolytic viral products makes them far out of reach for most patients. Here by analyzing the impact of intratumoral (IT) administrations of the trivalent live attenuated measles, mumps, and rubella viruses (MMR) vaccine, we unveil the cellular and molecular basis of MMR-induced anti-cancer activity. Strikingly, we found that IT delivery of low doses of MMR correlates with tumor control and improved survival in murine hepatocellular cancer and colorectal cancer models via increased tumor infiltration of CD8+ granzyme B+ T-cells and decreased macrophages. Moreover, our data indicate that MMR activates key cellular effectors of the host's innate and adaptive antitumor immunity, culminating in an immunologically coordinated cancer cell death. These findings warrant further work on the potential for MMR to be repurposed as safe and cost-effective cancer immunotherapy to impact cancer patients globally.

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MMR in mCRPC

Project description:MMR defects study in mCRPC using targeted DNA repair panel

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

Project description:High correlation was observed between T cell responses to SARS-CoV-2 and MMR and Tdap vaccine proteins in infected and uninfected individuals; the overlapping T cell population contained an effector memory T cell subset previously implicated in protective anti-viral immunity and their activation required APC-derived IL-15, known to sensitize T cells to activation. We were able to detect cross-reactive TCR repertoire in antigen experienced T cells recognizing SARS-CoV-2, MMR and Tdap epitopes using clonotyping and scRNA-seq. Indices of disease severity were reduced in MMR or Tdap vaccinated individuals by 32-38% and 20-23% respectively, among 73.582 COVID-19 positive patients.

2021-08-02 | GSE181046 | GEO

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

Project description:Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other group, and shared a relatively similar expression profile with POLE group by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 3371 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.

2022-03-09 | GSE193430 | GEO

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Project description:H441 cells lacking DNA MMR activity have reduced expression of antiviral and stress response genes during influenza A virus infection.

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Systems biology of immunity to MF59-adjuvanted versus non-adjuvanted trivalent seasonal influenza vaccines in early childhood

Project description:Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in ninety 14-24 month old healthy children.

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Time series of global gene expression after trivalent influenza vaccination in humans (female cohort)

Project description:The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells before and at three time points after the administration of a trivalent influenza vaccine in human female subjects, and to relate these to the antibody response to the vaccine

2013-06-18 | GSE48023 | GEO

Complete Genome Sequences of the Three African Horse Sickness Virus Strains from a Commercial Trivalent Live Attenuated Vaccine.

Project description:This is a report of the complete genome sequences of plaque-selected isolates of each of the three virus strains included in a South African commercial trivalent African horse sickness attenuated live virus vaccine.

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