Bispecific Antibody Targeting T-cell TGFb Signaling for Cancer Immunotherapy

SK2017-097

Bispecific Antibody Targeting T-cell TGFb Signaling for Cancer Immunotherapy

SK2017-097

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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.

ADVANTAGES

  • 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 

MARKET OPPORTUNITY

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. 

PATENT INFORMATION

Provisional application pending

LEAD INVESTIGATOR

Ming Li, PhD, Laboratory Head, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering

CONTACT INFORMATION

Eileen Flowers, PhD

Senior Licensing Manager
Tel: 646-888-1067
E-mail: flowerse@mskcc.org

Stage of Development

In vitro