On April 8, 2025 A team of researchers from the Rice Biotech Launch Pad at Rice University reported it has developed an implantable "cytokine factory" that safely triggers potent immune responses against hard-to-treat cancers, including metastatic melanoma, pancreatic and colorectal tumors (Press release, Rice University, APR 8, 2025, View Source [SID1234651841]).

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The study, published in The Journal of ImmunoTherapy of Cancer, details how an immunoprotected device near the tumor microenvironment containing cells engineered to locally release interleukin-12 (IL-12) — an "IL-12 cytokine factory" — successfully induces the recruitment of specialized immune cells called precursor exhausted T cells (Tpex cells). This Tpex cell recruitment results in a large, durable population of tumor-targeting T cells with broad molecular profiles, both in isolation and in an enhanced manner when implemented in combination with other immunotherapy approaches.

The IL-12 cytokine factories in combination with checkpoint inhibitors successfully eliminated local and distal tumors in preclinical models of metastatic melanoma and colorectal and pancreatic cancers. In addition to this robust efficacy signal, the IL-12 cytokine factory demonstrated safety in both mouse and nonhuman primate models.

This published research will serve as the foundation for an investigational new drug application (IND) with the U.S. FDA in early 2026, and RBL LLC expects to launch an emerging biotech company centered on the groundbreaking IL-12 cytokine factory technology.

"We designed the IL-12 cytokine factory to enhance immunotherapy approaches while minimizing toxicity, a critical need in the treatment of particularly aggressive cancers," said Omid Veiseh, professor of bioengineering, faculty director of the Rice Biotech Launch Pad and senior corresponding author of the publication. "IL-12 is particularly impactful compared to other cytokines, as our research demonstrates that other cytokines primarily recruit homogeneous T cell populations and show reduced efficacy over time, while IL-12 generates a more robust antitumor response by recruiting a more durable, broader repertoire of tumor-targeting T cells.

"We are incredibly grateful to ARPA-H for their support in advancing this groundbreaking project and are hopeful that this technology will significantly impact the lives of cancer patients by enhancing the efficacy of immunotherapy approaches in the clinic."

"Harnessing the cellular immune system to target solid tumors is a common but often fraught approach to fighting cancer as the associated challenge of efficacious treatment without toxicity remains elusive," said Nathan Reticker-Flynn, assistant professor of otolaryngology at Stanford University. "Our study demonstrates not only the efficacy of this technology in preclinical models but also its safety profile, which is a critical aspect as we move toward clinical trials. This research represents an important step forward in the quest to provide more effective treatments for patients battling metastatic cancers."

The research was supported through an Avenge Bio Sponsored Research Award to Rice, the Cancer Prevention Research Institute of Texas (RR160047), the National Institutes of Health (R01CA272769, DP2 AI177915) and ARPA-H (AY1AX000003). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding institutions.

Full Publication Details:

Title: IL-12-producing cytokine factories induce precursor exhausted T cells and elimination of primary and metastatic tumors

Journal: The Journal of ImmunoTherapy of Cancer

Corresponding Authors: Omid Veiseh

Full Author List: Amanda M. Nash, Jonathon DeBonis, Danna Murungi, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D. Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A. Igoshin, Jose Oberholzer, H. Courtney Hodges, Nathan Reticker-Flynn and Omid Veiseh