A New Way to Seed Immunotherapy Inside Pancreatic Tumors
Summary
- University of Miami Miller School of Medicine researcher Vineet Gupta is developing a novel immunotherapy strategy to help immune cells stay embedded inside pancreatic tumors.
- A prestigious Hirshberg Foundation grant supports his work on engineering tissue‑resident memory T cells to overcome immune resistance.
- The platform could open new doors for treating pancreatic cancer and other immune‑cold solid tumors.
Pancreatic cancer is notoriously resistant to immunotherapy. Unlike tumors that teem with immune cells ready to be activated, pancreatic tumors are often immune deserts — hostile, exclusionary environments where even the most powerful treatments struggle to gain a foothold.
A new project led by Vineet Gupta, Ph.D., a research assistant professor of surgery at Sylvester Comprehensive Cancer Center, part of University of Miami Miller School of Medicine, aims to change that landscape, cell by cell.
Dr. Gupta has been awarded a highly competitive 2025 Hirshberg Foundation Seed Grant for Pancreatic Cancer Research. The one‑year, $75,000 award supports early‑stage, high‑risk ideas with the potential to transform how pancreatic cancer is treated. His project, “Empowering Immunotherapy through Tissue‑Resident Memory T Cell Recruitment in Pancreatic Cancer,” takes a novel approach. Instead of simply unleashing immune cells, it focuses on helping the right immune cells stay put.
Re‑engineering Immune Memory Inside the Tumor
At the center of Dr. Gupta’s work are tissue‑resident memory T cells, or Trm cells. This specialized subset of immune cells embed themselves within tissues and provide long‑term, localized immune surveillance. In other cancers, Trm cells have been linked to improved responses to immunotherapy and more durable tumor control. In pancreatic cancer, however, they are scarce.
Dr. Gupta’s strategy is designed to change that.
The Hirshberg grant will support development of an antibody–siRNA conjugate (ARC) platform engineered to guide the fate of activated CD8⁺ T cells, nudging them toward a tissue‑resident memory state and encouraging their retention within pancreatic tumors. By selectively silencing molecular signals that drive T cells away from tissues, the platform aims to seed tumors with immune cells capable of sustained antitumor activity. Conceptually, the strategy functions like a targeted firmware update, reprogramming immune cells with new instructions so they remain engaged at the tumor site rather than defaulting to systemic circulation.
“These cells don’t just pass through,” Dr. Gupta said. “They stay, they adapt to their environment and they remember.”
From Immune Exclusion to Immune Engagement
Pancreatic ductal adenocarcinoma (PDAC) is widely regarded as one of the most immunologically complex and resistant cancers. Dense stroma, suppressive signaling pathways and limited immune infiltration all conspire to blunt the effects of checkpoint inhibitors such as anti‑PD1 and anti‑CTLA4 therapies.
“What excites me about Dr. Gupta’s approach is the deliberate reprogramming of tissue‑resident memory T cells to overcome barriers of immune exclusion,” said Nagaraj Nagathihalli, Ph.D., associate professor in the DeWitt Daughtry Family Department of Surgery and assistant director of basic science research at the Sylvester Pancreatic Cancer Research Institute, who serves as the project’s scientific mentor. “This work is mechanistically innovative and directly aligned with the unmet clinical challenges we face in PDAC.”
Under Dr. Nagathihalli’s mentorship, Dr. Gupta’s team will test the ARC platform across multiple preclinical pancreatic cancer models, including subcutaneous, orthotopic and genetically engineered systems. The goal is not only to measure tumor control, but also to understand how Trm cell density reshapes immune activity within the tumor microenvironment and whether that shift can sensitize tumors to existing immunotherapies.
A Modular Platform With Broader Reach
The work builds on earlier collaboration with Eli Gilboa, Ph.D., professor emeritus of microbiology and immunology at the Miller School, whose lab helped demonstrate that targeted inhibition of the transcription factor Klf2 in activated T cells promotes Trm differentiation and improved tumor control in vivo.
Now, with support from the Hirshberg Foundation, Dr. Gupta is extending those findings into pancreatic cancer, one of the most challenging proving grounds for immunotherapy innovation.
“Checkpoint inhibitors have transformed care for many cancers, but not for pancreatic cancer,” Dr. Gupta said. “By reshaping the immune ecosystem inside the tumor, we hope to change the rules of engagement.”
Importantly, the ARC platform is modular and antigen‑specific, allowing for multiplexed siRNA delivery and adaptive immune tuning. While pancreatic cancer is the immediate focus, the approach could be adapted to other immune‑cold solid tumors, including lung, colorectal, and melanoma cancers where immunotherapy responses remain inconsistent.
Seeding the Future of Translational Immunotherapy
The Hirshberg Seed Grant reflects Sylvester’s emphasis on cross‑disciplinary, translational research and supporting early‑career investigators with ideas that push beyond incremental advances.
As part of the award, Dr. Gupta will present his findings at the 2027 Hirshberg Foundation Scientific Symposium at UCLA and at the American Pancreatic Association annual meeting, further elevating Sylvester’s national presence in pancreatic cancer immunotherapy research.
“Mentorship is about building research that lasts beyond the lab,” Dr. Nagathihalli said. “Dr. Gupta’s work exemplifies a next‑generation immunotherapy mindset, one that could reshape how we think about immune memory, tumor resistance and durable cancer control.”
Tags: CAR T cells, DeWitt Daughtry Family Department of Surgery, Dr. Nagaraj Nagathihalli, Dr. Vineet Gupta, immunology, immunotherapy, Newsroom, pancreatic cancer, Sylverster Comprehensive Cancer Center