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Chimeric Antigen Receptors for the treatment of leukemia and other cancers.

09:11 EDT 13 Sep 2018 | NIH

Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody derived binding fragment fused to signaling domains.  The antibody derived binding fragment allows for the recognition of cancer associated targets and the signaling domains are T cell signaling domains that are components required for T cell activation.  When CARs are expressed on a T cell, they allow the T cell to specifically identify and eliminate malignant cancer cells.  This is a promising new therapeutic approach known as adoptive cell therapy.

FLT3 (a.k.a.,  Fms-Related Tyrosine Kinase 3) is a tumor-associated antigen that is known to be expressed on the cell surface of a majority of infant acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).  This technology concerns the development of CARs comprising an antigen-binding fragment derived from a FLT3 targeting antibody.  The resulting CARs can be used in adoptive cell therapy treatment for ALL or AML and other tumors which express FLT3.

IC: 
NCI
NIH Ref. No.: 
E-133-2016
Advantages: 
  • Some patients experience loss of expression of other surface antigens, such as CD19 which leads to disease relapse.  Therefore, alternative targets for the targeting ALL will be necessary for treating ALL.  As FLT3 is commonly activated by mutations that occur in both ALL and AML, it is likely an important pathway for leukemia making it less likely to be lost during treatment and hence an attractive target for CAR T cell therapy.  Mutations most commonly occur in the intracellular portion of FLT3 so the FLT3 CAR, which recognizes the extracellular portion of FLT3, will be able to target both wild type and mutant FLT3.
  • Infant ALL and AML patients have dismal prognoses from standard treatment and these populations are enriched for FLT3 expression, making them good candidate populations for FLT3 CAR therapy.
Applications: 
  • Treatment of cancers associated with FLT3, including ALL and AML and may include any FLT3 over-expressing leukemia.
Development Status: 

Discovery (Lead Identification)

Updated On: 
Jul 19, 2018
Provider Classifications: 
Publications: 
Patent Application: 
62/342,394
Patent Authority: 
U.S. Provisional
Licensing Contacts: 
Lead Inventor: 
Inventor IC: 
NCI
NCI
Inventor Lab URL: 
https://ccr.cancer.gov/pediatric-oncology-branch/terry-j-fry
LPM FIrst Name: 
John
LPM Last Name: 
Hewes
Inv Is lead: 
LPM Phone: 
240-276-5515
LPM Suffix: 
Ph.D.
LPM Organization: 
NCI - National Cancer Institute
DTDT Classification: 
Therapeutics
DTDT Description: 
Therapeutics
Pat Filing Date: 
2016-05-27
Collaboration Sought: 
Yes
Institute or Center: 
Collaboration Opportunity: 

Licensing and research collaboration

E Number Only: 
E-133-2016
Inventor First Name: 
Terry
Christopher
Inventor Last Name: 
Fry
Chien

Original Article: Chimeric Antigen Receptors for the treatment of leukemia and other cancers.

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