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Engineering T Cells as Possible Pancreatic Cancer Treatment

Posted on Tuesday, March 12, 2024

Pancreatic cancer has the highest mortality rate of all major cancers. ARCS Scholar Cara-lin Lonetree’s research focuses on the genetic engineering of CD8 T cells to generate a novel and effective treatment for this cancer. She is pursuing her PhD in Immunology at the University of Minnesota.

Lonetree studies the immune system and how it responds to cancer. “When people think about cancer treatment, chemo and radiation most likely come to mind,” she explains. “But those treatments don’t work for all types of cancer. Another option is immunotherapy, which uses the patient’s own immune system to fight cancer.”

“T cells can be removed from the blood and engineered to recognize and kill tumor cells when re-infused into the patient,” Lonetree states. “T cells are a crucial part of the immune system that fights off foreign viruses and bacteria, as well as cells that have become cancerous.”

Some T cell therapies are FDA-approved, but only for blood cancers. Solid tumors, such as pancreatic cancer, are much more challenging to treat. Lonetree says, “I’m trying to figure out how to best engineer the cells by adding in proteins that help and taking away those that don’t, to keep the T cells happy and healthy and functional within the tumor itself, which is very immunosuppressive.”

“There are a lot of factors within solid tumors, especially pancreatic cancer, that shut these cells down. There’s a lot of work underway to prevent this from happening, and to keep the T cells functioning in a challenging environment,” she continues. Her work is made possible by decades of previous research on gene delivery and DNA editing in mammalian cells.

Lonetree is engineering tumor-specific T cells to continuously produce signaling molecules, called cytokines, to support the T cells and other beneficial immune cells to boost the overall antitumor response. She uses in vivo mouse models and various in vitro cell culture assays to screen for improved T cell health and reduced tumor growth.

 As a second-year PhD student and mother, Lonetree is doing research and her course requirements while raising three children ages nine and under. “It’s definitely challenging, but at the same time, I’m grateful to be in this life stage,” she says.

The ARCS Scholar Award made it possible for Lonetree to travel to Italy for a conference “which was amazing, the International Cancer Immunotherapy Conference in Milan,” Lonetree says. She hopes to use ARCS funding to participate in the Association for Cancer Immunotherapy’s Winter School, an opportunity for select early-stage scientists to discuss their research with leaders in the field.

She hopes her research will contribute to advances in treating pancreatic cancer and other solid cancer tumors. “This patient population is in dire need of effective treatment options,” she says, “and I want nothing more than to help give them that.”