PROBLEM

Cancer immunotherapies (e.g. ICB, CAR-T cells, and conventional bispecific T cell engagers) have transformed treatment of hematological and solid malignancies; however, their impact is limited by several factors including insufficient durability of therapeutic activity, tumor heterogeneity, and highly immunosuppressive tumor microenvironments. Regulatory T cells (Tregs) and TGF-β signaling suppress anti-tumor immune responses and contribute to resistance and relapse. Current approaches do not effectively address both the tumor cells and immunosuppressive mechanisms simultaneously, thus highlighting the critical unmet need for therapies that can deliver durable, targeted immune activation while overcoming tumor-driven immune suppression.

SOLUTION

Dr. Zihai Li at OSU has developed a novel AAV8-delivered bispecific T cell engager (BiTCE) that simultaneously targets GARP on both tumor cells and Tregs, while engaging CD3 on T cells to drive cytotoxic activity. This dual-targeting strategy disrupts the GARP–TGF-β axis, reduces immunosuppressive Tregs, and activates effector T cells within the tumor microenvironment. Delivery via AAV8 enables sustained in vivo expression of BiTCE, thus overcoming the short half-life limitations of traditional biologics and enabling long-term immune engagement. Preclinical in vivo studies demonstrate robust anti-tumor activity across both solid tumors (glioblastoma) and hematological malignancies (lymphoma), with durable tumor control and favorable safety profile.

APPLICATIONS

• Monotherapy or combination therapy with existing ICB or CAR-T therapies to treat:
  • GARP-expressing solid tumors including glioblastoma (GBM)
  • GARP-expressing hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (B-ALL)

ADVANTAGES

• Triple targeting mechanism: eliminates 1) GARP+ malignant cells and 2) immunosuppressive Tregs, and simultaneously 3) drives durable cytotoxic responses with maintained T cell viability
• Overcomes resistance: disrupts the GARP–TGF-β axis to mitigate immune evasion in the tumor microenvironment
• Favorable safety profile: preclinical models demonstrate strong anti-tumor effects without significant toxicity or cytokine storms
• Versatile therapeutic platform: combines the therapeutic benefits of biologics and gene therapy delivery

Seeking opportunities for out-licensing, co-development, and collaboration