Several malignancies associated with a poor prognosis such as lung, pancreatic and colorectal cancers frequently harbor constitutively active KRAS mutants, which play a pivotal role in oncogenesis. Currently, there are no potentially curative treatments against most mutant KRAS harboring cancers once they become metastatic and unresectable. Despite intensive efforts to develop potent mutant KRAS inhibitors, none have shown a significant improvement to patients.
Researchers at NCI’s Surgery Branch have used their expertise in T-cell based therapies to develop a T cell receptor (TCR) that specifically recognizes G12D KRAS, a common driver of oncogenesis. This invention offers an alternative therapy to direct inhibition of mutant KRAS that has been demonstrative to be an effective treatment for advanced melanoma, lymphoma and sarcomas. The inventors have demonstrated that lymphocytes expressing the engineered TCR selectively target pancreatic G12D KRAS cells.
The NCI seeks co-development or licensing partners to extend the research toward in vivo efficacy testing and clinical trials.