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

Summary
Adoptive T Cell Therapy (ACT) has proven to effectively treat established tumors. This treatment consists of harvesting Tumor Infiltrated Lymphocytes (TIL) which specifically recognize cancer, expanding the tumor-specific TIL in vitro, and then reinfusing these cells into the patient for treatment. Both these lymphocytes and their T cell receptors (TCR) are valuable for cancer immunotherapy. Inventors from the National Cancer Institute (NCI) have developed an improved method to identify tumor-specific TCRs by reprogramming TIL into stem cells. This invention is available to license further development.
NIH Reference Number
E-091-2019
Product Type
Keywords
  • Immunotherapy, Adoptive T Cell Therapy, ACT, Tumor Infiltrated Lymphocytes, TIL, T-cell Receptors, TCR, Induced Pluripotent Stem Cells, iPSC, Vizcardo
Collaboration Opportunity
This invention is available for licensing.
Contact
Description of Technology

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
  • 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
Competitive Advantages
  • 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
Inventor(s)

Raul Vizcardo (NCI), Meghan L. Good (NCI), Rafiqul Islam (NCI ), Naritaka Tamaoki (NCI), Nicholas P. Restifo (NCI)

Development Stage
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]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/957,939 , Filed 07 Jan 2020
Therapeutic Area
Updated
Wednesday, March 4, 2020