Gamma Delta T Cell Engager platform (GADLEN)
Design and Structure
About the GADLEN Platfrom
Gamma delta T cells represent approximately 2% to 5% of the total T cell population, and their presence within tumors is strongly correlated with increased survival in cancer patients. Unlike alpha beta T cells which recognize tumor antigens presented on major histocompatibility complex molecules, gamma delta T cells are activated by a newly-identified, tissue-specific complex of two heterodimerized butyrophilin proteins. The therapeutic utilization of gamma delta T cells represents a novel approach for the treatment of cancer, as it presents an opportunity to treat checkpoint refractory patients with a fundamentally new modality.
We have leveraged our in-house expertise in protein engineering and intellectual property to build our novel Gamma Delta T Cell Engager, or GADLEN, platform to harness gamma delta T cells for the treatment of cancer. This is Shattuck’s second, wholly owned, platform to solve a biological problem by creating a therapeutic that matches the native structure of the target.
GADLEN compounds are comprised of two distinct fusion protein chains, with an engineered Fc linker domain that facilitates heterodimerization between the two chains. The compounds consist of extracellular domains of butyrophilin proteins on one side which are linked to tumor antigen specific single chain antibody fragments on the opposite side.
GADLEN compounds are designed to facilitate targeting of specific gamma delta T cells to tumor cells expressing a defined antigen. We believe our GADLEN platform offers a novel approach to the treatment of cancer.