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