Engineered T Cells that Target Tumor-Specific Mutations


Scientists at the National Cancer Institute's Surgery Branch have developed a method to identify and generate T-cell receptor (TCR) engineered T- cells for personalized cancer therapy. The TCR is a complex of integral membrane proteins that recognizes antigens and activates T cells. Human cancers contain genetic mutations that are unique in each patient. The researchers found cancer-specific mutations by sequencing tumors and comparing with normal cells. Using tandem minigene constructs encoding all of the patient's tumor mutations, they first identified T cells that were reactive with the unique mutated antigens expressed only in the patient's tumors. Next, they isolated the mutation-reactive TCRs and engineered peripheral blood T cells from the same patient to express these mutation-reactive TCRs. These personalized TCR engineered T cells can be expanded and infused back into the same patient with the potential to induce tumor regression.



Potential Commercial Applications: Competitive Advantages:
  • Personalized immunotherapy to treat primary and recurrent epithelial cancer.
  • A research tool to identify patient-specific immunogenic mutations in tumors.
  • A research tool to identify and isolate mutation-specific T cell receptors.  
 
  • 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 TCR engineered T cells target tumor cells 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 T cells expressing mutation-specific TCRs may maximize therapy and result in regression of all target lesions.


Development Stage:
Pre-clinical (in vivo)

Inventors:

Eric Tran (NCI)  ➽ more inventions...

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

Paul Robbins (NCI)  ➽ more inventions...

Steven Rosenberg (NCI)  ➽ more inventions...


Intellectual Property:
Foreign Filed Application No. PCT/US2014/05879

Publications:
E. Tran et al. PMID 24812403
P. Robbins et al. PMID 23644516
E. Tran et al. PMID 25046408
A. Gros et al. PMID 24667641

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-229-2014
Updated: Aug 31, 2016