Human cancers contain genetic mutations that are unique to each patient. Some of the mutated peptides are immunogenic, can be recognized by T cells, and may serve as therapeutic targets. However, there are technical barriers making it difficult to engineer tumor-specific T cells unique to each patient. Thus, there is a need for new methods of producing these T cells in sufficient quantities to provide patients with adoptive cell immunotherapy.
Researchers at the National Cancer Institute (NCI) have developed a method that enables the GMP manufacture of gammaretroviral vectors encoding tumor mutation-specific T Cell receptors (TCRs) using transient transfection-based vector production methods. This approach encompasses the production of a fully validated 293GP master cell bank (MCB). The 293GP is a 293-based retroviral packaging cell line stably expressing the Moloney Murine Leukemia Virus gap-pol gene. This MCB has been biosafety tested to industry standards, including: testing for replication competent retrovirus (RCR), human viruses and other adventitious virus. This MCB will be used to produce a transient pMSGV1 gammaretrovirus encoding a TCR reactive to a patient-specific neoantigen. Vector supernatants will be manufactured for a single patient and used to transduce the patient's autologous peripheral blood lymphocytes; thereby generating a cell therapy product for use in a single patient.
The NCI, Surgery Branch, is seeking statements of capability or interest from parties interested in licensing this invention and/or collaborative research to further develop, evaluate or commercialize this method of manufacturing vectors encoding cancer mutation-specific TCRs for adoptive cell immunotherapy.
- Personalized cell therapy targeting tumor specific mutations using gene modified T cells
- High efficiency production of GMP-compliant viral vectors
- Method for generating autologous high frequency (up to 90%) tumor mutation-specific T-Cells directed against mutations expressed by the patient’s tumor
Steven A Feldman (NCI), Steven A Rosenberg (NCI)
- U.S. Provisional: U.S. Provisional Patent Application Number 62/639,272 , Filed 06 Mar 2018