Reprogrammed Tumor Infiltrated Lymphocytes for Efficient Identification of Tumor-Antigen Specific T-Cell Receptors


Adoptive T Cell Therapy (ACT) is a form of cancer immunotherapy. It consists of harvesting Tumor Infiltrated Lymphocytes (TIL), screening for TIL which display tumor antigen-specific T-cell receptors (TCR), expanding these in vitro, and reinfusing into the patient for treatment. While ACT has proven effective in treating various cancer types, it is a laborious procedure as the harvested TIL population has generally limited expansion and a finite lifespan.

Researchers at the National Cancer Institute (NCI) Surgery Branch improved identification and isolation of the tumor antigen-specific TCR by reprogramming TIL into induced pluripotent stem cells (iPSC). As these TIL-iPSC can expand indefinitely but still retain the ability to differentiate into any cell type and the ability to encode TCRs, this method addresses previous limitations. Further, the expressed TCRs show a high affinity to their targets and can be used in ACT.   

NCI is seeking proposals from parties interested in licensing opportunities regarding this improved method to identify antigen-specific TCRs by reprogramming a bulk population of TIL.



Potential Commercial Applications: Competitive Advantages:
  • Technology could increase the clinical benefit of T-cell therapies beyond Tisagenlecleucel (Kymriah) for the treatment of several forms of leukemia and lymphoma and axicabtagene ciloleucel (Yescarta) was for the treatment of several types of relapsed or refractory large B-cell non-Hodgkin lymphomas (NHLs), including diffuse large B-cell lymphoma (DLBCL)
  • Identification of tumor specific TCRs for ACT
  • Identification of viral or bacterial antigen specific TCRs to treat infections
  • Identification of endogenous TCRs causing autoimmunity in patients
  • This method may be adapted to other immune cells and receptors, such as B cells, for therapy or antibody production purposes
 
  • Clinically significant expansion of reprogrammed TIL increasing efficiency of antigen-specific TCR identification
  • Clinically significant expansion technology has the potential for higher dosing and more treatments per collection
  • Potentially greater efficacy, as TCRs obtained using this technology retain polyclonality and display high affinity to their targets


Development Stage:
Discovery (Lead Identification)

Inventors:

Raul Vizcardo (NCI)  ➽ more inventions...

Meghan Good (NCI)  ➽ more inventions...

Rafiqul Islam (NCI)  ➽ more inventions...

Naritaka Tamaoki (NCI)  ➽ more inventions...

Nicholas Restifo (NCI)  ➽ more inventions...


Intellectual Property:
Application No. 62/957,939

Publications:
Vizcardo R, et al. Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells.  PMID 23290135
Maeda T, et al. Regeneration of CD8alphabeta T cells from T-cell-derived iPSC imparts potent tumor antigen-specific cytotoxicity.  PMID 27872100
Minagawa A, et al. Enhancing T cell receptor stability in rejuvenated iPSC-derived T cells improves their use in cancer immunotherapy.  PMID 30449714

Collaboration Opportunity:

Licensing only


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-091-2019
Updated: Mar 4, 2020