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.
- 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.
Eric Tran (NCI), Yong-Chen W. Lu (NCI), Paul F. Robbins (NCI), Steven A. Rosenberg (NCI)
- PCT: PCT Application Number PCT/US2014/058805, Filed 02 Oct 2014