biostudies-literatureShalabi HIntramural NIH HHSNCI NIH HHSNIH HHS451-463https://www.ebi.ac.uk/biostudies/studies/S-EPMC9353146biostudies-literatureUnknown140(5)Remission durability following single-antigen targeted chimeric antigen receptor (CAR) T-cells is limited by antigen modulation, which may be overcome with combinatorial targeting. Building upon our experiences targeting CD19 and CD22 in B-cell acute lymphoblastic leukemia (B-ALL), we report on our phase 1 dose-escalation study of a novel murine stem cell virus (MSCV)-CD19/CD22-4-1BB bivalent CAR T-cell (CD19.22.BBζ) for children and young adults (CAYA) with B-cell malignancies. Primary objectives included toxicity and dose finding. Secondary objectives included response rates and relapse-free survival (RFS). Biologic correlatives included laboratory investigations, CAR T-cell expansion and cytokine profiling. Twenty patients, ages 5.4 to 34.6 years, with B-ALL received CD19.22.BBζ. The coBloodCD19/22 CAR T cells in children and young adults with B-ALL: phase 1 results and development of a novel bicistronic CAR.PMC9353146S10 OD027023ZIA BC01182375N91019D00024ZIA BC011923Silbert SSu AAchar SShalabi HLittle LSteinberg SMTaylor NAhlman MInglefield JToledo-Tamula MAChien CDGoldberg SDeDe KHighfill SLSchneider DShahani SAFry TJMackall CLWang YMartin SAltan-Bonnet GBenzaoui MPanch SPouzolles MMolina JCShah NNLee DWWang HWFoley TLigon JAQin HYuan CMYates BWolters PLStroncek DfalseCD19/22 CAR T cells in children and young adults with B-ALL: phase 1 results and development of a novel bicistronic CAR.Remission durability following single-antigen targeted chimeric antigen receptor (CAR) T-cells is limited by antigen modulation, which may be overcome with combinatorial targeting. Building upon our experiences targeting CD19 and CD22 in B-cell acute lymphoblastic leukemia (B-ALL), we report on our phase 1 dose-escalation study of a novel murine stem cell virus (MSCV)-CD19/CD22-4-1BB bivalent CAR T-cell (CD19.22.BBζ) for children and young adults (CAYA) with B-cell malignancies. Primary objectives included toxicity and dose finding. Secondary objectives included response rates and relapse-free survival (RFS). Biologic correlatives included laboratory investigations, CAR T-cell expansion and cytokine profiling. Twenty patients, ages 5.4 to 34.6 years, with B-ALL received CD19.22.BBζ. The co2022-01-01T00:00:00Z2022 Aug2026-07-14T19:34:10.329Z2025-04-05T16:05:27.171ZS-EPMC93531463560518410.1182/blood.2022015795