Now that two COVID-19 mRNA vaccines have been adopted as tools to end the pandemic, its developers are looking for ways to apply the technology to other diseases. They include Pfizer’s COVID vaccine partner, BioNTech, which now has new data on one of the mRNA therapies it is developing for cancer.
A team led by BioNTech designed an mRNA cocktail that instructed cells to produce four anti-cancer molecules. Treatment suppressed tumors in mouse models of colon cancer and melanoma, and worked even better when combined with control point inhibition, the journal Translational Medicine reported.
The mRNAs of the experimental treatment code for cytokines interleukin-12 (IL-12), interferon-alpha, granulocyte-macrophage colony stimulating factor, and IL-15 sushi. These cytokines are known to help the immune system fight cancer. But their short half-life makes them difficult to administer to patients as treatments, as they can be toxic.
Preclinical studies have shown that administering cytokines directly to tumors with gene therapy could be a viable approach, but that it can also trigger unwanted side effects, the scientists explained in their study.
“In contrast, mRNA is an ideal therapeutic to ensure transient and local translation of cytokines, which can be administered with or without specialized formulation and adjusted for translation and activity in innate immune receptors,” they wrote. in the document.
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The researchers injected the mRNA mixture into colon tumors and melanoma in 20 mice. Treatment stopped the growth of the tumor and caused a complete regression of the cancer in 17 of the animals, they reported.
They then combined the mRNA cocktail with anti-CTLA-4 or anti-PD-1 inhibitors. This strengthened antitumor effects as well as tumor regression.
Among the co-authors of the BioNTech study were researchers from Sanofi, which has partnered with the mRNA pioneer to develop the therapy. Both companies have launched a phase 1 basket trial of the drug, called SAR441000, in patients with solid tumors. They are testing it both alone and in combination with Libtayo, a PD-1 inhibitor launched by Sanofi and Regeneron last year.
SAR441000 joins a long list of mRNA-based oncology projects at BioNTech. The company is also in phase 2 trials of BNT122, a melanoma treatment associated with Roche. And it has a dozen other anti-cancer drugs under development to address prostate cancer, triple negative breast cancer and several other types of solid tumors.