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 engineered bispecific antibody can stimulate patient T cell expansion by the T cell binding CD3 and CD28, while the antibodyâs heparin-binding domain (HBD) can augment retroviral binding to the T cell. These engineered antibodies can bind both T cell antigens and the viral vector, providing a less costly and efficacious alternative to coated beads and RetroNectin. By cutting the manufacturing expense, this antibody contributes to reducing the cost of CAR-T therapy.
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).
- Engineered bispecific antibodies are a less costly, modifiable and efficacious alternative to coated beads and RetroNectin® for gene transfer.
- 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 the engineered bispecific antibodies could be estimated from the savings generated by eliminating Dynabeads® and RetroNectin® for a total savings of $21,454.
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