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. 

Competitive Advantages:

• 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

Commercial Applications:

• 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