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.

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.

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.