SUMMARY OF INVENTION
TGFb is a multifunctional cytokine which inhibits the function of T-cells. Production of TGFb by activated CD4+ cells leads to suppression of anti-tumor immunity. Researchers have engineered a novel bispecific antibody (“4T-Trap”) targeting TGFb signaling in CD4+ helper T-cells for use as a potentially first-in-class immunotherapy drug.
MSK investigators observed that blocking TGFb signaling in helper T-cells was able to revive helper T-cell responses. In preclinical studies with 4T-Trap, MSK investigators have found that inhibition of TGFb signaling in helper T-cells elicits a novel anti-tumor immune response. 4T-Trap induced tumor vasculature reorganization and inhibited vessel leakage, causing cancer cell death. Initial findings demonstrate that 4T-Trap elicits a novel anti-tumor immune response distinct from that induced by immune checkpoint inhibitors including PD1 and CTLA4, which primarily target cytotoxic T lymphocytes. Investigators have demonstrated encouraging in vivo data in a mouse model of breast cancer.
- Potentially first-in-class immunotherapeutic drug
- Technology relies upon a distinct mechanism-of-action, by targeting helper T-cells that modulate the tumor stroma rather than tumor cells themselves
The market size for global cancer immunotherapies was valued at $58 billion in 2018 and is increasing rapidly, with growing adoption of advanced and novel cancer therapies. There is, however, a strong unmet need for novel immunotherapeutic approaches, since many patients fail to respond to current alternatives. Triple negative breast cancer patients, who account for 10%~20% of all breast cancer patients, offer one compelling example. MSK investigators are initially targeting this indication, since 4T-Trap-based immunotherapy has been shown to inhibit tumor growth in a murine model of breast cancer refractory to immune checkpoint therapies.
Provisional application pending
Ming Li, PhD, Laboratory Head, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering
Eileen Flowers, PhD