Improved CD22 Binders for Effective Immunotherapy Against Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

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.

Potential Commercial Applications:		Competitive Advantages:
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

Development Stage:
Pre-clinical (in vivo)

Related Invention(s):
E-106-2015


Inventors:

Dimiter Dimitrov (NCI)  ➽ more inventions...

Zhongyu Zhu ()  ➽ more inventions...

Terry Fry ()  ➽ more inventions...

Sneha Ramakrishna ()  ➽ more inventions...


Intellectual Property:
Application No. 62/697,185
Application No. PCT/US2019/041401

Publications:
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

Collaboration Opportunity:
Licensing only


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-161-2018
Updated: Jun 30, 2020