T-Cell Therapy Against Patient-Specific Cancer Mutations


Human cancers contain genetic mutations that are unique to each patient. Some of the mutated peptides are immunogenic, can be recognized by T cells, and therefore, may serve as therapeutic targets.

Scientists at the National Cancer Institute's Surgery Branch developed a method to identify T cells that specifically recognize immunogenic mutations expressed only by cancer cells. The scientists identified cancer-specific mutations from a patient with widely metastatic cholangiocarcinoma by sequencing tumor samples and comparing with normal cells. Using tandem minigene constructs encoding all of the mutations expressed by a patient's tumor, the inventors identified T cells that recognized the immunogenic mutations from the same patient. These mutation-reactive T cells have the potential to eliminate the cancer cells while sparing normal tissues since normal tissues do not express the mutations. The mutation-reactive T cells were expanded in vitro, and then infused as a highly pure population back into the same patient. The patient experienced tumor regression when treated with this approach.



Potential Commercial Applications: Competitive Advantages:

- Personalized immunotherapy with mutation-reactive T cells for mediating tumor regression in patients with immunogenic mutations.
- Mutation-reactive T cell therapy especially beneficial for cancer patients refractory to other therapies.
- A research tool to identify patient-specific immunogenic mutations in the tumor.

 

- This patient-specific therapy has the potential application to most epithelial cancers, which account for about 90% of cancer deaths in the United States.
- Personalized mutation-specific T cells recognize mutations harboring tumor cells only and spare normal tissues. This therapy has no tissue toxicities comparing to traditional chemotherapy and radiotherapy. 
- The infusion of a highly pure population of these mutation-specific T cells may maximize therapy and result in regression of all target lesions.



Development Stage:
Clinical

Inventors:

Eric Tran (NCI)  ➽ more inventions...

Yong-Chen Lu (NCI)  ➽ more inventions...

Paul Robbins (NCI)  ➽ more inventions...

Steven Rosenberg (NCI)  ➽ more inventions...


Intellectual Property:
U.S. Filed Application No. PCT/US2014/058796

Publications:
Tran E, et al. PMID 24812403
Robbins P, et al. PMID 23644516
Tran E, et al. PMID 25046408

Collaboration Opportunity:

Licensing and research collaboration


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-233-2014
Updated: Aug 31, 2016