Leveraging immune memory against measles virus as an antitumor strategy in a preclinical model of aggressive squamous cell carcinoma

J Immunother Cancer, 2021 · DOI: 10.1136/jitc-2020-002170 · Published: January 1, 2021

Simple Explanation

The study explores using pre-existing immunity to measles virus (MeV) to fight cancer. Researchers engineered squamous cancer cells to express MeV antigens and then tested if MeV-vaccinated mice could reject these tumors. The approach involves redirecting pre-existing viral immunity to target tumors. This is achieved by forcing the expression of specific viral antigens within the tumor cells, making them recognizable to the immune system. The use of mRNA encoding the cognate antigens, delivered directly into the tumor, significantly enhanced overall survival in mice, even resulting in complete tumor regression in some cases.

Study Duration

Not specified

Participants

4–6-week-old female C3H/He mice

Evidence Level

Preclinical model

Key Findings

1
MeV vaccination generated cytotoxic T lymphocyte (CTL) immunity in mice, demonstrated by enhanced interferon gamma production and antigen-specific T cell proliferation.
2
Mice vaccinated against measles virus rejected tumors engineered to express measles antigens at a significantly higher rate (77%) compared to control groups (21%).
3
Intratumoral injection of mRNA encoding measles antigens, complexed with Viromer nanoparticles, significantly enhanced overall survival and induced complete tumor regression in 25% of mice.

Research Summary

This study demonstrates the feasibility of redirecting pre-existing viral immunity against measles virus (MeV) to inhibit tumor growth in a preclinical model of aggressive squamous cell carcinoma. The approach involves vaccination to establish MeV immunity, followed by challenging the mice with tumor cells engineered to express MeV antigens, resulting in significant tumor rejection. Direct intratumoral delivery of mRNA encoding MeV antigens using Viromer nanoparticles led to enhanced survival and tumor regression, suggesting a potential therapeutic strategy.

Practical Implications

Novel Cancer Immunotherapy

Redirecting pre-existing viral immunity represents a novel approach to cancer immunotherapy, potentially complementing existing strategies like personalized vaccines and checkpoint inhibitors.

Therapeutic Target

Measles virus antigens can be used as therapeutic targets in cancers, especially in individuals with pre-existing immunity to the virus.

mRNA Delivery

Viromer nanoparticles offer an effective means of delivering mRNA encoding viral antigens directly into tumors, enhancing the therapeutic effect.

Study Limitations

1
Incomplete understanding of the ongoing immune responses in this therapeutic setting.
2
The model used C3H/He mice engrafted with SCCVII cells, which may not fully represent the complexity of human tumors and immune responses.
3
A current limitation of intratumoral immunotherapy approaches is the need for repeated injections.

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