Discovery (Lead Identification)
T cells with T cell receptors (TCRs) for cancer-specific antigens are used for adoptive cell therapy (ACT), wherein a patient’s T cells are redirected against their own cancer. However, these isolated T cells may require further ex vivo manipulation to enhance their anti-tumor activity. The ex vivo manipulation of these T cells, or the selection of less functionally inert T cells, and genetic insertion of tumor specific TCRs may circumvent these limitations.
To address this issue, it is crucial to recognize, select, and isolate tumor reactive T cells from a plethora of other non-reactive ones. When re-infused into the patient, non-reactive T cells may impede the effectiveness of an immunotherapy. However, the current methodologies to identify, select, and isolate these tumor reactive T cells, are laborious, time-consuming, and cost intensive.
Researchers at the National Cancer Institute (NCI) have developed a novel method which isolates and sequences tumor reactive TCRs from cancer specific T cells using calcium ion (Ca2+) flux as the marker of TCR ligation and activation. TCRs identified by this method were found to be tumor specific and can be used to redirect the patient’s T cells against potential tumor targets. This method requires minimal manipulation, and drastically reduces the time and cost of the tumor specific TCR identification and isolation process. NCI seeks research co-development partners and/or licensees for this invention.