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.
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.
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.
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