Novel Cancer Immunotherapy: A T Cell Receptor That Specifically Recognizes Common KRAS Mutations

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.

Potential Commercial Applications: Competitive Advantages:
  • T-cell therapy to treat a variety of cancers that harbor KRAS mutations, in particular, G12D mutation
  • Therapy for cancers that harbor additional constitutively active KRAS mutations


  • Proven therapeutic strategy for targeting cancers that harbor mutant target proteins
  • Alternative strategy to previously unsuccessful small molecule KRAS inhibitors

Development Stage:
Discovery (Lead Identification)

Related Invention(s):


James Yang (NCI)  ➽ more inventions...

Intellectual Property:
US Provisional Application No. 62/084,654

Collaboration Opportunity:

Licensing only

Licensing Contact:
John Hewes, Ph.D.
Phone: 240-276-5515

OTT Reference No: E-028-2015
Updated: Dec 7, 2017