Chimeric antigen receptor T cell (CAR-T) therapy re-engineers T cells from cancer patients to target tumor antigens. However, expanding these cell populations can take several weeks, and involves the use of reagents such as DynabeadsÂ®, and efficient CAR-T construct transduction with retroviral vectors requires reagents like RetroNectinÂ®. An artificial antigen-presenting cell (APC) can stimulate patient T cell expansion by the T cell binding CD3 and CD28 expressed on the APC, while the aAPCâs heparin-binding domain (HBD) can augment retroviral binding to the T cell. These aAPCs can induce equivalent proliferation as DynabeadsÂ®, and the HBD can replace RetroNectinÂ® with comparable viral transduction efficiency. APCs should shorten the timeframe for therapeutic intervention and diminish the projected cost.
- Current technologies for T lymphocyte expansion involve Dynabeads® CD3/CD28 paramagnetic beads ($11,360), which have been known to reduce CAR-T yields due to tight binding after T-cell stimulation. Following expansion, efficient viral transduction of the T cells with the CAR-T construct has typically required using RetroNectin® Recombinant Human Fibronectin ($10,094).
- aAPCs with a HBD can be synthesized without great expense, stimulate greater yields of lymphocytes than Dynabeads® in as little as six days, and can replace RetroNectin®. There is no need to kill aAPCs prior to injection, as they are initially irradiated to prevent cell division, and later killed by the activated patient T cells.
- The marketplace is attractive for the development of improved CAR-T methodologies, as dozens of clinical trials are currently being carried out by a number of companies including Kite Pharma, Juno Therapeutics, Cellectis, Bellicum Pharmaceuticals, Ziopharm Oncology, and Bluebird Bio. The price for aAPCs could be estimated from the savings generated by eliminating Dynabeads® ($11,360), RetroNectin® ($10,094), and the recombination-competent retrovirus screening which is not required for viral incubations under four days ($15,000) for a total savings of $36,454.