Targeting the CD22 receptor of B-cells with chimeric antigen receptor (CAR)-T cells has been a promising new therapy to treat B-cell malignancies in clinical trials, inducing remission in 70% of patients with relapsed acute lymphoblastic leukemia (ALL). However, diminished CD22 expression on B-cell surface can lead to relapse and decreased remission duration, which may be prevented through increasing CAR-T affinity towards CD22. Researchers at the National Cancer Institute (NCI) developed an affinity-matured monoclonal antibody panel including an anti-CD22 antibody variant, L7, displaying a higher affinity against CD22 than the non-affinity matured versions. The inventors at the NCI developed CAR-T cells incorporating the L7 variable fragment and observed prolonged remission using the L7-CAR-T treatment in combination with Bryostatin1-induced CD22 expression in vivo. The L7 antibody can also be used in other antibody-based therapeutics (such as antibody drug conjugates) against B-cell malignancies.