Chimeric Antigen Receptors (CARs) for Treating Lymphoma and Other Cancers

Abstract:

Chimeric antigen receptors (CARs) are hybrid proteins that consist of two major components: a targeting domain and a signaling domain.  The targeting domain allows T cells which express the CAR to selectively recognize and bind to diseased cells that express a particular protein.  Once the diseased cell is bound by the targeting domain of the CAR, the signaling domain of the CAR activates the T cell, thereby allowing it to kill the diseased cell.  This is a promising new therapeutic approach known as adoptive cell therapy (ACT).

Researchers at the NCI Experimental Transplantation and Immunology Branch developed a CAR that recognizes human tumor necrosis factor receptor superfamily member 8 (TNFRSF8, also known as CD30). The expression of CD30 is deregulated in a variety of human cancers, including many lymphomas.  By creating a CAR that recognizes CD30, it may be possible to treat these cancers using adoptive cell therapy.

Competitive Advantages:

• Human components are less likely to cause adverse or neutralizing immune response in patients
• Targeted therapies decrease non-specific killing of healthy cells and tissues, resulting in fewer off-target side-effects and healthier patients

Commercial Applications:

• Treatment of human cancers associated with expression of CD30 or variants thereof
• Specific cancers include: Non-Hodgkins Lymphomas, Hodgkin's Lymphomas, several solid malignancies