University of Minnesota researchers have secured USD 2.08 million in renewed NCI funding to develop off-the-shelf immune cell therapies built around an unusual strategy: engineering regulatory T cells to kill cancer rather than suppress immune responses.
The award supports a three-project, four-core program led by principal investigator John E. Wagner in the Department of Pediatrics. The program targets persistent barriers in adoptive cell therapy — T cell exhaustion, tumor antigen escape, on-target/off-tumor toxicity, and the cost and time constraints that limit access to individualized manufacturing — by developing allogeneic cell products capable of industrial-scale production.
The scientific strategy centers on three engineered cell platforms. Project 1 focuses on allogeneic CD4 regulatory T cells (Tregs) equipped with synthetic stimulatory receptors and drug-inducible chimeric antigen receptors (CARs), designed to allow pharmacological control over CAR activity and reduce exhaustion risk. Project 2 targets acute myeloid leukemia (AML) using CD83 CAR-expressing iPSC-derived CD8 iTregs — a renewable cell source derived from induced pluripotent stem cells (iPSCs) — engineered to resist rejection and exhaustion while retaining tumoricidal activity. Project 3 combines engineered iPSC-derived natural killer cells (iNK cells) with trispecific killer engagers (TriKEs) and CARs to improve specificity, persistence, and potency against AML.
Prior-period findings cited in the grant abstract include demonstrated tumoricidal activity of engineered Tregs comparable to conventional T cells, successful generation of iPSC-derived CD8 iTregs amenable to genetic modification, and iNK cells co-expressing a high-affinity non-cleavable CD16a and membrane-bound interleukin-15/IL-15 receptor without CD38, the company said — a configuration the team reported enhances in vivo persistence and permits selective depletion of regulatory cells using anti-CD38 antibodies. The program also reported achieving manufacturing runs capable of producing hundreds to thousands of cell doses, a scale relevant to commercial viability.