Cell Lines that Constitutively Express High-Frequency KRAS and P53 Mutations and Human Leukocyte Antigens (HLAs)
Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes tumor infiltrating lymphocytes (TILs) or genetically engineered T cells to attack tumor cells through recognition of tumor-specific antigens. A major hurdle in the development of ACT is the identification and isolation of T cells that recognize antigens that are expressed by tumor cells but not by healthy tissues. Current methods to identify such T cells involve extracting autologous antigen presenting cells (APCs) from patients in an expensive, laborious, and time-consuming process. In addition, the quantity and quality of extracted APCs varies significantly between patients, necessitating a novel, standardized approach.
Researchers at the National Cancer Institute (NCI) developed a library of cell lines to identify T cells that specifically target tumor cells, thus eliminating the need for autologous APCs. These cell lines stably express tumor-specific antigens at a high level in the tandem minigene (TMG) format. The antigens expressed arise from mutations in the RAS or p53 genes. These mutations are also referred to as “hotspot” driver mutations because they are shared among many cancer patients and are the most commonly mutated genes in solid tumors. The cells also stably and highly express Class-I or Class-II human leukocyte antigens (HLAs) of interest, allowing for determination of HLA restriction. These cell lines offer a versatile, quick, and cost-effective method to identify, isolate, and expand tumor-reactive T cells.
The NCI seeks parties interested in licensing this library of cell lines stably expressing tumor-specific antigens and HLAs.
- Rapid identification, isolation, and expansion of mutated RAS or p53-reactive TILs or TCR-engineered T cells
- Validation of mutated RAS or p53-reactive TILs or TCR-engineered T cells
- Determination of HLA restriction of mutated RAS or p53-reactive TILs or TCR-engineered T cells
- Identification of T cell reactivities in infectious diseases (ex. Influenza, COVID-19)
- Identification of T cell reactivities in immunological disorders
- Universal APCs
- Replace the expensive, laborious, and time-consuming process of extracting/preparing autologous APCs
- Express tumor-specific antigens in the tandem minigene (TMG) format, allowing the cell lines to cover multiple different RAS or p53 mutations
- Express hotspot driver mutations, granting applicability to a broad range of cancer patients