NIH Funds Programmable mRNA to Treat Cancer

(NIEHS, nih.gov)

4 Aug. 2021. National Cancer Institute is funding research on using programmable synthetic messenger RNA to treat two types of solid tumor cancer. Strand Therapeutics Inc. in Cambridge, Massachusetts is receiving two small business set-aside grants of about $400,000 each from NCI, an agency of National Institutes of Health, to advance the company’s work on supplemental therapies for triple-negative breast cancer and melanoma.

Strand Therapeutics is a four year-old enterprise, spun-off from the synthetic biology lab of Ron Weiss at MIT. The company’s technology is based on synthetic messenger RNA, or mRNA, designed to express therapeutic proteins over longer periods of time, and produce precise immune-system responses. In addition, Strand Therapeutics says its mRNA therapies can be programmed to respond only under certain conditions, such as in a cancerous tumor, as well as treat multiple diseases with a single drug.

The NIH funds aim to further develop Strand’s technology to show in preclinical tests it can supplement immunotherapy drugs to treat triple-negative breast cancer and melanoma. In triple-negative breast cancer, tumors do not express hormonal or HER2 receptor proteins that are targets for most breast cancer drugs. Melanoma is an aggressive type of skin cancer, which while not as common as basal cell and squamous cell skin cancers, is more likely to spread to other parts of the body.

Strand Therapeutics says many immunotherapies for solid tumor cancers use antibodies to block checkpoint inhibitors, allowing the immune system to attack tumor cells. However, the response rate for triple-negative breast cancer to these immunotherapies is low, and for many people with melanoma treated with these drugs, the relapse rate is high. The company plans to produce synthetic mRNA therapies that express cytokine proteins, similar to those produced by immune system cells, but designed to work only in the tumors.

Demonstrate therapeutic feasibility

“It is well known that cytokines can be utilized to achieve an anti-tumor effect in cancer patients,” says Strand Therapeutics co-founder and CEO Jake Becraft in a company statement released through BusinessWire. “However, treatment strategies that involve cytokines can be highly toxic, and therefore, its efficacy can be limited. To that end, we can use our programmable, self-replicating mRNA therapeutic platform to localize cytokine expression that will potentially enable more precise and longer-lasting anti-cancer immune responses.”

In the triple-negative breast cancer project, Strand is designing a form of mRNA that expresses cytokine proteins resembling interleukin-12 produced by natural killer and T-cells in the immune system. The transcribed mRNA, says the company, is delivered in lipid nanoparticles that respond to the chemistry of the tumor’s microenvironment, the surrounding matrix that supports tumor development, but not elsewhere in the body, to reduce off-target effects. In addition, the lipid nanoparticles interact with the mRNA payloads to increase their impact on tumor cells.

For the melanoma, project, Strand Therapeutics is designing a similar form of mRNA, but in this case expressing two types of cytokines, first interleukin-12 and later interleukin-15. This combination of cytokines, says the company, aims to provide a more durable response, while limiting toxicity to other parts of the body. In both the breast cancer and melanoma projects, Strand plans to conduct tests with lab mice to demonstrate the treatments’ therapeutic feasibility.

The awards are Small Business Innovation Research or SBIR grants made under NIH’s small business programs that set aside a part of the agency’s research funding for U.S.-based and owned companies. SBIR grants in most cases are made in two parts: a first phase to determine technical and commercial feasibility, and a second phase to develop and test a working prototype or prepare for clinical trials. These grants are first-phase awards.

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