Bispecific Chimeric Antigen Receptors to CD22 and CD19 for Treating Hematological Cancers


Chimeric antigen receptors (CARs) are hybrid proteins that have antibody binding fragments fused to protein signaling domains that activate T cells. The antibody binding fragments allow the CAR to recognize specific cell types, thereby activating the T cell through the protein signalling domain. Once activated, the T cells selectively eliminate the cells which they recognize. By engineering a T cell to express CARs with antibody binding fragments which are specific for cell surface proteins that are associated with diseased cells, it is possible to treat the disease. This is a promising new therapeutic approach known as adoptive cell therapy.

CD22 and CD19 are cell surface proteins that are expressed on a large number of B cell lineage hematological cancers, such as leukemia and lymphoma. CD19 CAR T cells have demonstrated potent activity against leukemia in early clinical trials. However, some of these patients will relapse with leukemia that no longer expresses the CD19 protein. This technology concerns the use of two high affinity antibody binding fragments as the targeting moieties of a CAR: one to CD22 (m971), and one against CD19 (FMC63). The resulting CAR can be used in adoptive cell therapy treatment for cancers which express either CD22 or CD19.

Potential Commercial Applications: Competitive Advantages:
  • Treatment of diseases associated with increased or preferential expression of CD22 or CD19.
  • Specific diseases include hematological cancers such as chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL) acute lymphoblastic leukemia (ALL) and lymphoma.
 
  • High affinity of the m971 and FMC63 antibody binding fragments increases the likelihood of successful targeting.
  • Targeted two antigens expressed on the same type of diseased cells may increase efficacy relative to targeting a single antigen.
  • Targeted therapy decreases non-specific killing of healthy, essential cells, resulting in fewer non-specific side-effects and healthier patients.
  • Hematological cancers are susceptible to cytotoxic T cells because they are present in the bloodstream.


Development Stage:
  • In vitro data available
  • In vivo data available (animal)


Related Invention(s):
E-080-2008-0
E-291-2012-0


Inventors:

Rimas Orentas (NCI)  ➽ more inventions...

Crystal Mackall (NCI)  ➽ more inventions...

Terry Fry (NCI)  ➽ more inventions...


Intellectual Property:
US Application No. 62/135,442
PCT Application No. PCT/US2016/023055
US Application No. 15/559,485

Publications:
Lee DW, et al. PMID 25319501
Haso W, et al. PMID 23243285

Licensing Contact:
James Knabb, Ph.D.
Email: jim.knabb@nih.gov
Phone: 240-276-5530

OTT Reference No: E-106-2015-0
Updated: Aug 22, 2018