Providence Cancer Institute secures three significant grants

Federal research funding has never been harder to win considering tighter budgets and fierce competition for every dollar. Yet, against that backdrop, Providence Cancer Institute has hit a trifecta - three grants and three funding sources. Although each study takes a different approach, the question they ask is the same: How do we get the immune system to do what it is supposed to do to fight cancer?

The first of the three prestigious grants was awarded to researchers at Providence Cancer Institute in May. The National Institutes of Health (NIH) R01* of $3.4M over five years will help uncover the mechanistic "why" behind the unusually high response rates seen with neoadjuvant immunoradiotherapy (NIRT) - the combination of immunotherapy with highly focused, lymphatic-sparing radiation delivered before surgery - in head and neck cancer. The research team, led by R. Bryan Bell, M.D., D.D.S., director of Earle A. Chiles Research Institute and executive medical director of Providence Cancer Institute, along with Thomas Duhen, Ph.D., Brian Piening, Ph.D., and their team will use the grant to study why lymph node preservation helps tumors respond to neoadjuvant treatment, and why some tumors respond while others resist it.

NIH R21 to unmask a hidden trick tumors play on the immune system

This summer, Thomas Duhen, Ph.D., was awarded an NIH R21 grant of $437,311** over multiple years to fund research into a newly identified mechanism in colorectal cancer. Dr. Duhen is an associate member at Earle A. Chiles Research Institute and director of the Anti-Cancer Immune Response Laboratory. R21 grants support early-stage, exploratory research that can open the door to bigger studies in the future.

Dr. Duhen's work centers on a type of immune cell called a regulatory T cell. Normally, these cells act like brakes on the immune system, keeping it from attacking the body's own healthy tissue. But Dr. Duhen's research suggests that in colorectal tumors, this braking system may be turned against the immune response that is supposed to be fighting cancer.

"This R21 grant provides a unique opportunity for my lab to explore the origin of tumor-reactive regulatory T cells in patients with colorectal cancer," Dr. Duhen said. "Our work will investigate whether the tumor environment hijacks the anti-tumor immune response thus impairing its efficacy." Uncovering this mechanism would offer a novel angle to reset the anti-tumor immune response in patients."

Colorectal cancer is one of several cancers where immunotherapy has struggled to gain traction. If Dr. Duhen and his team can pinpoint how tumors flip this immune switch, it could point toward new ways to make immunotherapy work for patients who currently have limited options.

Stand Up To Cancer grant to arm T-cell therapy against pancreatic cancer's defenses

Another exciting grant awarded this summer comes from Stand Up To Cancer (SU2C). Eric Tran, Ph.D., associate member at Earle A. Chiles Research Institute and director, Adoptive Cell Therapy Laboratory, and his collaborator, Di Liu, Ph.D., of Arizona State University, Tempe, AZ., have received a $225,000 Nina Nicolai Pancreatic Cancer Innovation in Collaboration Award, which is given to members of the SU2C scientific community to spur collaborative development of new pancreatic cancer treatments.

The treatment strategy being pursued by Drs. Tran and Liu targets tumors with KRAS mutations. But instead of inhibiting the activity of mutant KRAS proteins, it uses two types of immunotherapy, including an mRNA vaccine that serves 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.

Dr. Tran and his team at Providence Cancer Institute have developed this TCR T-cell therapy and tested different iterations of it in a small number of patients, with some encouraging results.

"This grant is a catalyst for a new inter-institutional collaboration to help advance this exciting work," Dr. Tran 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."
_{Research supported by a Stand Up To Cancer- Nina Nicolai Pancreatic Cancer Innovation in Collaboration Award , Grant Number (SU2C-AACR-PS-41).} <_o3a_p>

Find out more

Providence Cancer Institute is one of the leading providers of cancer care in Oregon and a global leader in immuno-oncology. Through its research division, the Earle A. Chiles Research Institute, patients have access to a vast clinical trial portfolio. Learn more about our clinical trials here.

*Research described here is supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA301042. The NCI has recommended $3,401,182 in total federal funding to support this five-year R01 project, subject to future funding availability and project performance. Federal funding is estimated to finance 81% of this project, with 19% of project costs financed by non-governmental funding. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

**Research described in this article is supported by the National Cancer Institute of the National Institutes of Health under Award Number R21CA292306. The NCI has awarded $437,113 in total federal funding to support this two-year project. Federal funding is estimated to finance 93% of this project, with 7% of project costs financed by non-governmental funding. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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