High-Throughput Generation of Induced Pluripotent Stem Cells Carrying Antigen-Specific T Cell Receptors from Tumor Infiltrated Lymphocytes


One form of adoptive T cell therapy (ACT) consists of harvesting tumor infiltrating lymphocytes (TIL), screening and isolating TIL which display tumor antigen-specific T-cell receptors (TCR), expanding the isolated T cells in vitro, and reinfusing them into the patient for treatment. While highly active in the treatment of certain cancers (e.g., melanoma), current methods used to produce cancer-reactive T cells require significant time and may not adequately identify the desired TCRs which bind cancer targets.

Researchers at the National Cancer Institute (NCI) Surgery Branch have developed a method which allows for the identification of TCRs from bulk populations of TIL. This method generates induced pluripotent stem cell (iPSC) lines inheriting tumor antigen-specific TCRs from minor populations of TIL, not routinely achievable by other conventional approaches. Additionally, the method can generate previously unidentified tumor antigen-specific iPSC lines without pre-generating tumor antigen-specific T cell lines. This novel method is an improvement in the generation of tumor antigen-specific TCR inherited iPSC lines.

NCI seeks proposals from parties interested in licensing this improved method for the development of cancer immunotherapies. 



Potential Commercial Applications: Competitive Advantages:
  • Therapeutics for a wide range of liquid and solid cancers
  • iPSC lines inheriting tumor antigen-specific TCRs from minor populations of TIL not routinely achievable by other conventional approaches
  • Improved and expedited cell therapy manufacturing, including:
    • Identification and reprogramming of bulk, polyclonal TIL populations with a high frequency of inherited tumor antigen-specific TCRs
    • Method to identify, clone, and transduce tumor and neoantigen-specific TCRs from a bulk, polyclonal TIL population by genomic DNA sequencing
    • Identification of tumor-reactive TCRs without having to identify their TCR alpha and TCR beta recombination patterns by bioinformatics and algorithm predictions

 

 
  • iPSC lines inheriting tumor antigen-specific TCRs from minor populations of TIL not routinely achievable by other conventional approaches
  • Production of several TIL-derived iPSC (TIL-iPSC) with multiple different and novel tumor antigen-specific TCRs
  • iPSC can be expanded without restrictions, and TCR sequencing and identification can be achieved with minimal error by genomic DNA based TCR sequencing
  • Improved generation of tumor antigen-specific TIL for T cell rejuvenation purposes and subsequent TIL-iPSC-derived immunotherapy

 



Development Stage:
Discovery (Lead Identification)

Related Invention(s):
E-091-2019


Inventors:

Raul Vizcardo (NCI)  ➽ more inventions...

SM Islam (NCI)  ➽ more inventions...

Naritaka Tamaoki (NCI)  ➽ more inventions...

Takuya Maeda (NCI)  ➽ more inventions...

Nicholas Restifo (NCI)  ➽ more inventions...


Intellectual Property:
Pat: - issued -

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-109-2020
Updated: Apr 28, 2021