DATE: November 7, 2017
TIME: 10:00AM PST
Chimeric Antigen Receptor (CAR)-transduced T lymphocytes have demonstrated impressive clinical activity against B cell malignancies in phase I trials. In most instances, lentivirus-based or a retrovirus-based gene vectors were used to introduce the therapeutic gene expression cassette into the genome of T lymphocytes. The gene expression cassette is composed of an internal promoter and the CAR, created by splicing together of extracellular antigen-binding motifs, linker and transmembrane domains, and intracellular lymphocyte signaling domains. This synthetic engineered receptor can be modified in a number of ways in order to further improve CAR T efficacy and safety. We have found that the combination of two extracellular binding domains is possible, thus expanding the antigens targeted by a single CAR construct, and potentially providing a more effective barrier to the generation of antigen-escape variants. Making CAR-based immunotherapy broadly available to those in need, requires the ability to isolate, activate, transduce, and expand T cell or NK cell populations in a safe clinically-relevant platform. The CliniMACS® Prodigy is a closed cell culture system that combines recent advances in lymphocyte isolation (using antibody-conjugated matrices), activation (using an anti-CD3/CD28 nanomatrix), and automated culture using optimized media and cytokines, into a single platform suitable for the introduction of therapeutic gene vectors, lymphocyte transduction, culture and expansion, and final formulation. Using clinical-grade lentivirus-based gene vectors we have demonstrated the ability to produce CAR-expressing T cells. The CliniMACS® Prodigy platform provides a standardized solution for broad application of CAR-based therapies in clinical studies.
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