Tri-specific killer engagers (trikes) for targeted cancer immunotherapy
Tri-specific Killer Engagers (TriKEs) enhance NK cell targeting of solid tumors by binding CD16 and B7-H3 antigens. Combined with IL-15, they boost T cell response, overcoming tumor-induced immune exhaustion. Validated in preclinical models, TriKEs show promise for cancer therapy.
Overview
Tri-specific Killer Engagers (TriKEs) are an innovative immunotherapy platform designed to enhance the targeting of solid tumors by natural killer (NK) cells. TriKEs employ a dual camelid single domain antibody to simultaneously bind CD16, a potent NK cell receptor, and B7-H3, a pan-solid tumor antigen. The inclusion of an IL-15 sequence between these domains further stimulates NK cells, aiding in overcoming hypoxia and immune exhaustion within the tumor microenvironment. This unique approach not only directly targets cancer cells but also orchestrates a T cell response, transforming the tumor into a more 'hot' environment conducive to immune attack.
Technical specifications
- TriKE Composition: Dual camelid single domain antibody targeting CD16 and B7-H3
- Stimulation Mechanism: Agonistic binding of CD16 with IL-15 co-stimulation
- Target Antigens: CD16 (NK cell receptor) and B7-H3 (solid tumor antigen)
- Functional Model: Demonstrated efficacy in preclinical models, specifically ovarian cancer, using NSG mice engrafted with human cancer cells
- Immune Response: Enhances NK cell activity and T cell migration, overcoming immune exhaustion and hypoxia
Technology readiness level
The TriKE platform has reached a Technology Readiness Level of 8, indicating it has been proven to work in preclinical settings and is nearing clinical integration. The next steps involve detailed validation in humanized mouse models to further assess efficacy and safety in human-relevant contexts.
About University of Minnesota
The University of Minnesota is a flagship, comprehensive public research university spanning multiple campuses, with a large research enterprise and clinical integration. Industry engages through co-located labs on the Twin Cities campuses, access to an academic health system for clinical translation, and pilot and field-testing facilities that speed scale-up. A statewide extension network and outreach centers provide real-world sites and data partnerships across Minnesota, while proximity to a dense medtech and Fortune 500 corridor enables frequent collaboration. Research is supported by competitive federal funding, including NIH, NSF, DOE, USDA, and DoD. A dedicated technology transfer office manages IP, licensing, sponsored research agreements, and startup incubation to speed commercialization.
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