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BioNTech mRNA Cancer Treatment Enters Human Trials

Being able to deliver cytokines directly to cancer cells may prove effective.

mRNAmRNA
 

The current pandemic has brought mRNA vaccines into the spotlight and have likely sped up the widespread adoption and usage of this technology. Now, a company has its sights set on treating cancer with mRNA technology, and the initial animal data is positive.

mRNA steps up to treat cancer

mRNA vaccines look like they are here to stay, and while probably best known thanks to the current pandemic, their development began years before this. The way they work gives them a great amount of utility, and now their application for other diseases is being explored. In particular, mRNA therapies have become a new focus for Pfizer’s vaccine partner, BioNTech, in developing a cancer treatment.

BioNTech has published data in the journal Science Translational Medicine for one of its mRNA cancer therapies for the treatment of colon cancer and melanoma. The data has been promising enough in these animal studies to prompt a move towards clinical trials.

The researchers created an mRNA cocktail that, once delivered to the target cells, prompts them to produce four anticancer molecules. In mouse models of colon cancer and melanoma, the treatment was able to suppress tumors. Even better, when the mRNA mix was combined with a checkpoint inhibitor, the results were further improved.

The mRNAs included in the cocktail code for four cytokines: interleukin-12, interferon-alpha, granulocyte-macrophage colony-stimulating factor, and IL-15 sushi. These particular cytokines were chosen due to how they support the immune system to combat cancer.

The short half-life of these cytokines makes their direct injection challenging as a treatment, and this method is potentially harmful. Previous studies have shown that delivering cytokines to tumors through gene therapy can work but carries the risk of side effects. Using mRNA gets around this problem, as it allows for the transient production of cytokines at the target cells.

What the study showed

In the study, the researchers administered the mRNA cocktail into colon and melanoma tumors in 20 mice. They reported that treatment was able to halt tumor growth, leading to total regression in 17 of the mice.

Following that, the researchers combined the mRNA mixture with either anti-CTLA-4 or anti-PD-1 checkpoint inhibitors. Adding either of these increased the anti-tumor effects as well as regression speed.

Based on this data, BioNTech and co-authors Sanofi have joined forces to further develop the approach. A phase 1 basket trial of the drug called SAR441000 is to begin enrolling patients with solid tumors. A basket trial tests how well a new drug works in patients who have different types of cancer but that share the same mutation or biomarker.

The trial will test the mRNA both solo and in combination with Libtayo, a PD-1 inhibitor launched by Sanofi and Regeneron last year.

Abstract

Local immunotherapy ideally stimulates immune responses against tumors while avoiding toxicities associated with systemic administration. Current strategies for tumor-targeted, gene-based delivery, however, are limited by adverse effects such as off-targeting or antivector immunity. We investigated the intratumoral administration of saline-formulated messenger (m)RNA encoding four cytokines that were identified as mediators of tumor regression across different tumor models: interleukin-12 (IL-12) single chain, interferon-a (IFN-a), granulocyte-macrophage colony-stimulating factor, and IL-15 sushi.

Effective antitumor activity of these cytokines relied on multiple immune cell populations and was accompanied by intratumoral IFN-? induction, systemic antigen-specific T cell expansion, increased granzyme B+ T cell infiltration, and formation of immune memory. Antitumor activity extended beyond the treated lesions and inhibited growth of distant tumors and disseminated tumors. Combining the mRNAs with immunomodulatory antibodies enhanced antitumor responses in both injected and uninjected tumors, thus improving survival and tumor regression. Consequently, clinical testing of this cytokine-encoding mRNA mixture is now underway.

Conclusion

The current pandemic has without a doubt propelled it into the spotlight, but the technology has been in development long before that arrived. Cancer is predominantly an age-related disease, so the development of mRNA therapies to treat it is most welcome. It is great to see it being used on cancer, and there could be many other uses for mRNA in the treatment of age-related diseases.

If you enjoyed this story you might also enjoy the Lifespan News show’s coverage of this too.

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About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. jimofoz
    September 18, 2021

    The yellow fever vaccine has also shown promise in driving immune anti tumor responses when directly injected into tumors in combination with systemic checkpoint blockade antibodies:

    Repurposing the yellow fever vaccine for intratumoral immunotherapy (2020):
    https://www.embopress.org/doi/full/10.15252/emmm.201910375

    It would actually be cool to see if there is any synergy by using these mRNAs for inflammatory cyctokines along with the yellow fever vaccine and systemic antibodies against PD1 and CTLA4.

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