Researchers have developed a novel chimeric antigen receptor (CAR) T-cell therapy that reduces toxicities commonly associated with the treatment—cytokine release syndrome (CRS) and neurotoxicity—without compromising efficacy, according to the study published in Nature Medicine.
“Toxicities are currently the biggest barrier to the use of CAR T-cell therapy,” said senior author Si-Yi Chen, MD, PhD, of the of the University of Southern California, in a statement. “My hope is that this safer version of CAR T-cell therapy could someday be administered to patients in outpatient settings.”
In this phase I preclinical trial, researchers generated a new anti-CD19 CAR molecule [CD19-BBz(86)]. “We found that CD19-BBz(86) CAR T-cells produced lower levels of cytokines, expressed higher levels of antiapoptotic molecules, and proliferated more slowly than the prototype CD19-BBz CAR T cells, although they retained potent cytolytic activity,” the authors wrote.
A "safe and potent" anti-CD19 CAR T cell therapy: 25 patients enrolled. CR rate of 24% for the entire cohort, although the abstract reports the CR rate for the highest dose cohort only. No CRS or ICANS >grade 1 #bmtsm #CARTcell https://t.co/U7p8UxwkHP
— Muzaffar Qazilbash (@Transplant_Doc) April 25, 2019
CAR T-cell Safe and effective treatment
This slower-moving and less toxic anti-CD19 CAR T-cell treatment was tested in 11 patients with B-cell lymphoma. Six patients (54%) who received a dose of 2×108–4×108 experienced complete remission (CR). The median duration of response among those who achieved CR was was greater than 181 days (range = 162-290 days). Five of these patients had ongoing CR at the time of publication.
Remarkable! What cytokines? They might be overrated for CAR-T effector function. A structure based design of safe and potent anti-CD19 CAR T cell therapy. https://t.co/5jkPXB5zpz
— Zihai Li, MD, PhD (@Zihai) April 27, 2019
No neurological toxicity or CRS grade ≥1 occurred in the 25 patients who received this treatment. “CD19-BBz(86) CAR T-cells persistently proliferated and differentiated into memory cells in vivo,” the researchers reported.
“Therapy with the new CD19-BBz(86) CAR T-cells produces a potent and durable antilymphoma response without causing neurotoxicity or severe CRS, representing a safe and potent anti-CD19 CAR T-cell therapy,” the researchers concluded.
The researchers intend to study this therapy further in a phase II, multicenter trial to assess the safety and efficacy in a larger patient cohort.