Report Details Novel Methods to Improve Clinical Use of CAR T-Cell Immunotherapies

In less than a decade, adoptive chimeric antigen receptor (CAR) T-cell therapies have yielded previously unseen frequencies of complete remissions in hematological indications, and CAR T-cell immunotherapies are promising potential treatments for a range of malignancies. Although promising, the use of CAR T-cell therapies faces challenges because of the complexity of their production and adverse events related to their activity, which range from mild to life-threatening.

Researchers led by Julien Valton, PhD, at Cellectis, Inc, recently reported the development of CubiCAR architecture, which has the potential to improve the safety of CAR T-cell immunotherapies for a broad range of patients.¹ Their study was published online June 12, 2018, in Scientific Reports.

CAR T-cell therapy uses a patient’s own blood to tease out the T-cells—a process called leukapheresis. Using a disarmed virus, the T-cells are then genetically engineered to produce specific CAR receptors on their surface, which allow the T-cells to recognize and attach to a specific protein (antigen) on tumor cells. Once the collected T-cells have been engineered to express the antigen-specific CAR, they are “expanded” in the laboratory into hundreds of millions of cells and are then infused into the patient. The engineered cells further multiply in the patient’s body and recognize and kill cancer cells that express the specific antigen on their surface.

The CubiCAR architecture is an all-in-one, tri-functional CAR architecture with an embedded multifunctional tag for CAR T-cell detection, purification, and on-demand depletion by rituximab (Genentech’s innovator, Rituxan), which is approved for cancer and autoimmune indications. According to the new report, CubiCAR T-cells were efficiently purified, retained their capacity to proliferate and specifically kill tumor cells, and were rapidly depleted by a clinically relevant dose of rituximab.

The investigators first demonstrated the versatility and broad applicability of CubiCAR T-cells in vitro before going on to investigate their anti-tumor activity and depletability in vivo in an immunodeficient BRGS mouse model. Cellectis Inc. [cellectis.com] uses its TALEN ultra-precise gene-editing technology to engineer primary T-cells to generate next-generation CAR T-cells used in adoptive therapies against cancer.

Reference

1. Valton J, Guyton V, Boldajipour B, et al. Chimeric antigen receptor T-cell immunotherapies. Scientific Reports. 2018;8(1):8972. doi:10.1038/s41598-018-27264-w.