Technology Bundle ID
NCI-E-168-2018

Calcium (Ca2+) Flux-Dependent Method to Detect and Isolate Tumor Reactive T Cell Receptors (TCRs)

Applications
Co-Inventors
Ana Pasetto (NCI)
Douglas Palmer (NCI)
Nicholas Restifo (NCI)
Steven Rosenberg (NCI)
Development Status
Discovery (Lead Identification)
ICs

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.

Commercial Applications
  • T-cell isolation for ACT or TCR therapy 
  • Personalized immunotherapy to treat cancer patients
  • Research tool to identify mutation-specific TCRs
Competitive Advantages
  • Rapid and cost-effective method for tumor specific TCR identification and isolation
  • Widely applicable to different types of cancers
  • Limited off-target effects
  • Patient-specificity to improve efficacy of ACT

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