Cambridge, Massachusetts-based GentiBio, Inc. has received a USD 1.07 million NIH R44 SBIR Phase II grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to advance an allogeneic, off-the-shelf engineered regulatory T cell (EngTreg) therapy for newly diagnosed type 1 diabetes (T1D). The award supports preclinical proof-of-concept, safety, and manufacturing feasibility studies intended to position the candidate for clinical translation. Principal investigator Gene Ichiro Uenishi leads the program.

The funding reflects continued NIH interest in cell-based immune tolerance strategies for T1D, a disease for which no curative therapy exists. Regulatory T cell therapy in T1D has faced persistent obstacles: autologous Treg products are costly to manufacture, difficult to scale, and have shown limited persistence and antigen specificity in early clinical experience. GentiBio's approach with GNTI-148 attempts to address those constraints simultaneously.

The candidate is built on the same platform underpinning the company's clinical-stage autologous product GNTI-122, which incorporates stable FOXP3 expression and a chemically inducible signaling complex (CISC) for tunable interleukin-2 (IL-2) signaling. GNTI-148 adds hypoimmune engineering — modifications designed to reduce or eliminate host immune rejection of allogeneic cells — enabling an off-the-shelf format without requiring patient-matched manufacturing. Pancreatic islet-specific targeting is also built into the construct, intended to concentrate suppressive activity at the site of autoimmune destruction rather than broadly dampening systemic immunity.

Several groups are pursuing Treg-based approaches in T1D. Academic and early-stage industry programs have explored both antigen-specific Tregs and polyclonal Treg infusions. GentiBio's differentiation rests on the combination of islet antigen specificity, stable FOXP3 engineering, CISC-mediated IL-2 control, and allogeneic manufacturability in a single construct.

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