(16MB049) APC: Artificial Antigen-Presenting Cells expressing CD3, CD28, and a Heparin-Binding Domain for Producing CAR-Ts

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 Dynabeads®, and efficient C…

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 Dynabeads®, and efficient CAR-T construct transduction with retroviral vectors requires reagents like RetroNectin®. 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 aAPC’s heparin-binding domain (HBD) can augment retroviral binding to the T cell. These aAPCs can induce equivalent proliferation as Dynabeads®, and the HBD can replace RetroNectin® with comparable viral transduction efficiency. APCs should shorten the timeframe for therapeutic intervention and diminish the projected cost.

Abstract:

  • 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.

Website:

https://moffitt.org/research-science/academic-and-industry-partnerships/office-of-innovation/available-technologies/immunotherapies/16mb049-aapc-artificial-antigen-presenting-cells-expressing-cd3-cd28-and-a-heparin-binding-domain-for-producing-car-ts/