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T-Cell Therapy Against Patient-Specific Cancer Mutations

Summary
Scientists at the National Cancer Institute developed a method to identify T cells that specifically recognize immunogenic mutations expressed only by cancer cells. NCI seeks parties interested in collaborative research to co-develop or license T-cell therapy against cancer mutations
NIH Reference Number
E-229-2014
Product Type
Keywords
  • T-cell, cholangiocarcinoma, immunogenic, Tran, Rosenberg
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

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
  • 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.
Competitive Advantages
  • 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.
Inventor(s)

Eric Tran (NCI), Yong-Chen W Lu (NCI), Paul F Robbins (NCI), Steven A Rosenberg (NCI)

Development Stage
Publications

Tran E, et al. [24812403]

Robbins P, et al. [23644516]

Tran E, et al. [25046408]

Patent Status
  • PCT: PCT Application Number PCT/US2014/058796, Filed 02 Oct 2014
Therapeutic Area
Updated
Monday, February 3, 2020