- Therapeutics
- Andy Burke
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.
- 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
Raul Vizcardo (NCI), SM Rafiqul Islam (NCI), Naritaka Tamaoki (NCI), Takuya Maeda (NCI), Nicholas P Restifo (NCI)
- Discovery (Lead Identification)
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]
- U.S. Provisional: U.S. Provisional Patent Application Number 63/068,458 , Filed 21 Aug 2020
- Cancer/Neoplasm
- Immune System and Inflammation