SUMMARY OF INVENTION
This technology seeks to expand the efficacy of CAR T-cell immunotherapies through use of a novel co-stimulatory domain that replaces the more commonly used 41BB or CD28. MSK investigators have developed CARs that encode a KIT domain in the cytoplasmic signaling pathway, which confers the CAR T-cell with improved proliferation and better cytotoxicity against low-antigen-expressing targets. This improved co-stimulatory domain can be part of any CAR T-cell, and it is believed that KIT CARs could be used in immunotherapies for many different types of solid and liquid tumors.
The KIT domain includes a mutation which has been shown to limit apoptosis and promote proliferation in mast cells. It is unique for a number of reasons, including that oncogenicity is established only in the presence of other mutations; it can signal without ligand/receptor interaction; and it is independent of SHP1/2 inhibition, and therefore has the potential to avoid PD-L1/2-PD-1 inhibition. Preliminary data indicates that KIT CARs proliferate only in the presence of antigen stimulation and that they are sensitive to switch pocket inhibitors already in clinical use to treat mast cell syndrome and KIT mutant cancers.
- Platform technology, with potential to significantly expand use of CAR T immunotherapies to those patients with solid and liquid tumors
- Compares favorably to current CARs, with improved proliferation and stronger cytotoxicity against low-antigen-expressing targets
- Ability to address unexpected cytotoxicity issues with “safety switches” already in clinical use
Once commercialized, CAR T-cell therapies are expected to provide treatment for millions of cancer patients, with market size projected to reach $8.5B by 2028. It is anticipated that KIT CARs could be used in many different types of CAR T-cell immunotherapies for solid and liquid tumors.
STAGE OF DEVELOPMENT
in vivo in multiple cancer models
PCT Application PCT/US2020/062992 pending, filed December 3, 2020.
LEAD INVESTIGATOR Prasad Adusumilli, MD, Deputy Chief, Thoracic Service, Memorial Sloan Kettering
Eileen Flowers, PhD
Senior Manager, Business Development & Licensing