Stand Up To Cancer announced the recipients of the SU2C Nina Nicolai Pancreatic Cancer Innovation in Collaboration Award.
The approximately $225,000 in award funding will support a multi-institutional research team developing a potential new treatment approach for pancreatic cancer that pairs an mRNA vaccine with a KRAS-targeted cellular therapy.
The collaborative project is being led by Eric Tran, of the Providence Cancer Institute, and Di Liu, of Arizona State University. Tran leads the Adoptive Cell Therapy Laboratory in Providence’s Earle A. Chiles Research Institute, and Liu is an assistant professor in ASU’s School of Molecular Sciences and Biodesign Institute.
“The Nicolai Award supports innovative collaborations that we believe have great potential to lead to effective new treatments for pancreatic cancer,” Julian Adams, SU2C president and CEO, said in a statement. “This year’s recipients embody the spirit of this award—a partnering of talented young scientists who are pursuing a promising and novel immunotherapy-based approach to treating this lethal disease.”
Researchers have trained much of their focus on a potential weak spot in pancreatic cancer: mutations in a gene called KRAS, which are present in tumors in nearly 90% of people with this disease. These mutations fuel the production of rogue proteins that help tumors grow and spread to other parts of the body.
Although mutant KRAS proteins were long thought to be “undruggable,” there are now two FDA-approved drugs to treat pancreatic cancer with KRAS-mutant tumors.
Both have had a modest clinical impact, however, with many patients’ tumors not responding to the treatment at all and resistance quickly setting in among most patients whose tumors do respond.
And despite a proven track record against many other types of cancer, immune-based treatments have not worked against pancreatic cancer. Therapies known as mRNA treatment vaccines may buck that trend, with promising results seen in small clinical trials.
The treatment strategy being pursued by Tran and Liu targets tumors with KRAS mutations, but not by inhibiting the activity of mutant KRAS proteins. Rather, it uses two types of immunotherapy, including an mRNA vaccine. But rather than serving as the primary treatment, the vaccine is being used as an immune booster to a TCR T-cell therapy.
The receptor on the TCR T-cell therapy is genetically engineered to bind to cancer cells with KRAS G12D mutations, which are present in about 40% of people with pancreatic cancer.
Tran and his team at Providence have developed this TCR T-cell therapy and tested different iterations of it in a small number of patients, with some encouraging results, including one person with metastatic pancreatic cancer who had a year-long response.
Liu and his colleagues at Arizona State bring to the project their expertise and experience in developing mRNA vaccines. Funding from the award will support their efforts to engineer an mRNA vaccine with a specialized Cap2 structure, a chemical feature at the front end of mRNA, that is designed to help maintain antigen production and, thus, provide sustained stimulation for KRAS G12D-directed TCR-T cell therapy.
“In the setting of cancer immunotherapy, vaccine-induced innate immune activation can be helpful for stimulating antitumor immunity, but can also suppress mRNA translation,” Liu said in a statement. “Our goal is to explore whether Cap2 mRNA can help maintain antigen production under these conditions and thereby better support TCR-T cell responses against pancreatic cancer.”
According to Tran, the Nicolai Award will provide a platform for the partnership.
“We already have proof-of-concept that TCR T-cell therapy can shrink tumors in patients with pancreatic cancer. This grant is a catalyst for a new inter-institutional collaboration to help advance this exciting work,” he said. “The resulting preliminary data will support future efforts to secure larger, long-term funding, ultimately accelerating our progress toward developing more effective treatments for patients with pancreatic cancer.”
Stand Up To Cancer’s scientific partner, the American Association for Cancer Research, will administer the grant.
