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.
- Adoptive immunotherapy for relapsed / refractory ALL
- Antibody drug conjugates against relapsed / refractory ALL
- Treatment of other B-cell malignancies
- An established, de-risked target as other anti-CD22 targeted therapies have reached and been evaluated in clinical trials
- Prolonged remission in ALL mouse models
- High affinity antibodies against CD22 can be used to develop targeted therapies
Dimiter Dimitrov Ph.D., ScD (NCI), Zhongyu Zhu Ph.D. (NCI), Terry Fry MD (NCI), Sneha Ramakrishna MD (NCI)
Haso W, et al. Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. [PMID 23243285]
Fry TJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. [PMID: 29155426]
Ramakrishna S, et al. Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence. [PMID: 31110075]
- U.S. Provisional: U.S. Provisional Patent Application Number 62/697,185 , Filed 12 Jul 2018
- PCT: PCT Application Number PCT/US2019/041401 , Filed 11 Jul 2019