Chimeric Antigen Receptors to CD22 for Treating Hematological Cancers

Abstract:

Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause T-cells which express the CAR to become cytotoxic.  Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize via the antibody binding fragment of the CAR.  Thus, by engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target those cells for destruction.  This promising new therapeutic approach is known as adoptive cell therapy.
 
CD22 is a cell surface protein expressed on a large number of B-cell lineage hematological cancers, such as leukemia and lymphoma.  Several promising therapies are being developed which target CD22, including therapeutic antibodies and immunotoxins.  This technology concerns the use of a high affinity antibody binding fragment to CD22 (known as m971), as the targeting moiety of a CAR. The resulting CAR can be used in adoptive cell therapy treatment for cancer.

Competitive Advantages:

  • High affinity of the m971 antibody binding fragment increases the likelihood of successful targeting
  • Targeted therapy decreases non-specific killing of healthy, essential cells, potentially resulting in fewer non-specific side-effects and healthier patients
  • Hematological cancers are susceptible to cytotoxic T-cells for treating because they are present in the bloodstream 
  • Expression of CD22 only on mature cells avoids stem cell elimination during treatment

 

Commercial Applications:

  • Treatment of diseases associated with increased or preferential expression of CD22
  • Hematological cancers such as chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL) and pediatric acute lymphoblastic leukemia (ALL)

 

Patent Information: