NIH and Stanford University researchers designed a Phase I study to evaluate a new treatment for relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL). Current practice relies on the use of chimeric antigen receptor (CAR) T cells that target CD19; however, antigen loss often prevents this approach from being effective. Because CD22 is also present in most B-ALL cases, but typically is retained following CD19 loss, investigators examined the clinical activity of CD22-targeted CAR immunotherapy. The trial included 21 patients, 17 of whom previously underwent CD19-focused immunotherapy. The new treatment path produced antileukemic effects, with complete remission achieved in 11 of the 15 study participants who were exposed to it—including all five whose disease was resistant to CD19-targeted immunotherapy. Responders remained in remission for a median 6 months.