Peter Cook, PhD, on Exploring DARIC CAR T-Cells for Autoimmune Indications

“We showed that by lentiviral transduction we can make cells that have equivalent activity to cells that express a traditional BCMA CAR, except that their activity is solely dependent on the presence of the dimerizer, which causes the CAR to come together. We showed that in vitro targeting multiple multiple myeloma cancer cell lines which express BCMA and then also in vivo in mice that have multiple myeloma tumor cells, the tumor is cleared by the DARIC CAR T-cells only if the mice are simultaneously dosed with the drug.”

Over the past few years, interest in applying chimeric antigen receptor T-cell (CAR-T) therapy approaches to autoimmune disease indications has rapidly grown. Many programs currently in development utilize approaches similar to those used in the FDA-approved CAR-T therapies for oncology indications. Although, some institutions are exploring more innovative CAR-T approaches in this field.

At the the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA, Peter Cook, PhD, a senior research scientist at Seattle Children’s Research Institute, presented preclinical research on the use of BCMA-directed dimerizing agent-regulated immune-receptor complex (DARIC) T-cells to target plasma cells. Although the approach was initially tested for ability to clear multiple myeloma cancer cells in vitro and in mice, Cook and his colleagues intend for it to eventually be applied to autoimmune indications such as the prevention of organ rejection in solid organ transplant.

In an interview with CGTLive® at the conference, Cook discussed the mechanism behind the approach and the rationale for its application. Notably, the approach uses a lentiviral vector to produce the CAR T-cells in vivo, but when they are initially generated, they are inactive. Only when a small molecule drug, Rapamycin, is administered, do the CAR T-cells become active. In addition to discussing the research itself, Cook also took time to acknowledge more generally the important work of the investigators at the Center for Immunity and Immunotherapies at Seattle Children's Research Institute.

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REFERENCE
1. Cook P. Targeting human plasma cells using small molecule regulated BCMA CAR T cells eliminates circulating antibodies in humanized mice. Presented at: at ASGCT 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA. Abstract #1258