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A New Target for CAR T Cells Achieves Remission in Resistant Pediatric B-ALL

Surabhi Dangi-Garimella, PhD
An early-stage trial in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has found that modifying the chimeric antigen receptor (CAR) T cells to target the CD22 receptor achieved remission.
An early-stage trial in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has found that modifying the chimeric antigen receptor (CAR) T cells to target the CD22 receptor achieved remission. The study, a collaboration between the Stanford University School of Medicine and the National Cancer Institute (NCI), has been published in Nature Medicine.

CAR T-cell treatments have seen significant progress over the last year, and the first CAR T product, tisagenlecleucel (Kymriah), manufactured by Novartis, received FDA approval in August. However, side effects, such as cytokine release syndrome, and affordability remain significant problems with this treatment.

The current study enrolled 21 children and young adults (7 to 30 years) with B-ALL, 17 of whom had previously failed on CD19-directed immunotherapy. Each patient had undergone at least 1 bone marrow transplant and a significant portion of patient who had previously received CD19-taregetd treatment no longer expressed CD19 on their cancer cells.

Following administration of varying doses of anti-CD22 CAR T cells, complete remission was observed in 11 of 15 patients (73%) who received at least 1 million CD22-CAR T cells per kilogram of body weight—the median duration of remission was 6 months. Relapse, the authors wrote, was associated with a reduced CD22 site density, which allowed CD22+ cells to escape being targeted and destroyed by CD22-CAR T cells.

“The take-home message is that we've found another CAR T-cell therapy that displays high-level activity in this phase 1 trial,” Crystal Mackall, MD, associate director of Stanford’s Cancer Institute and the director of the Parker Institute for Cancer Immunotherapy at Stanford, said in a statement. “But the relapse rate was also high. So, this forces the field to get even more sophisticated. How much of a target is needed for successful, long-lasting treatment? What happens if we target both CD19 and CD22 simultaneously?”

Follow-up studies are being designed by Mackall and co-author Terry Fry, MD, a pediatric hematologist and oncologist at the NCI, to address this question.

Reference

Fry TJ, Shah NN, Orentas RJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy [published online November 20, 2017]. Nat Med. doi: 10.1038/nm.4441.

 
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