Now that two mRNA COVID-19 vaccines have been embraced as tools to end the pandemic, their developers are looking for ways to apply the technology to other diseases. They include Pfizer’s COVID vaccine partner, BioNTech, which now has fresh data on one of the mRNA therapies it is developing for cancer.
A BioNTech-led team designed a cocktail of mRNAs that instruct cells to produce four cancer-fighting molecules. The treatment suppressed tumors in mouse models of colon cancer and melanoma, and it worked even better when combined with checkpoint inhibition, they reported in the journal Science Translational Medicine.
The mRNAs in the experimental treatment code for the cytokines interleukin-12 (IL-12), interferon-alpha, granulocyte-macrophage colony-stimulating factor and IL-15 sushi. These cytokines are known to assist the immune system in fighting cancer. But their short half-life makes them difficult to administer to patients as treatments, because they can be toxic.
Preclinical studies have shown that administering cytokines directly to tumors with gene therapy could be a viable approach, but that 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 delivered with or without specialized formulation and be further tuned for translation and activity on innate immune receptors,” they wrote in the paper.
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The researchers injected the mRNA mixture into colon and melanoma tumors in 20 mice. The treatment halted tumor growth, 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 checkpoint inhibitors. That strengthened the anti-tumor effects, as well as the tumor regression.
BioNTech’s co-authors on the study included researchers from Sanofi, which has partnered with the mRNA pioneer to develop the therapy. The two companies have launched a phase 1 basket trial of the drug, dubbed SAR441000, in patients with solid tumors. They are testing it both as a monotherapy 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 Roche-partnered melanoma treatment. And it has a dozen other cancer drugs in development addressing prostate cancer, triple-negative breast cancer and several other solid tumor types.