Question

Describe chimeric antigen receptors and how are they implemented and used in tumor immunotherapy?

Requirements: Be specific in terms of the components of the chimeric antigen receptor, the steps employed in the clinic and the resulting immune response towards the tumor cells.

Answer 1

Chimeric antigen receptors (CARs) are genetically engineered forms of T-cell receptor, which is expressed on the surface of T cells and allow the modified T cells to attach to specific proteins on the surface of cancer cells and thereby activating killing of these cells.  Chimeric antigen receptors typically consist of an antigen-binding domain (ectodomain), a transmembrane domain, and intracellular (endodomain) immune receptor tyrosine-based activation motifs.

Chimeric antigen receptor (CAR) T-cell therapy is a novel cancer treatment that modifies a patient’s own T cells to better recognize and kill the patient’s cancer.

• Blood from a vein in the patient’s arm flows through a tube to an apheresis machine which removes the white blood cells, including the T cells, and sends the rest of the blood back to the patient.
• The T cells are sent to a laboratory where they are genetically engineered to produce chimeric antigen receptors (CARs) on the surface of the cells.
• Millions of the CAR T cells are grown in the laboratory and then given to the patient by infusion.
• When they come in contact with their targeted antigen on a cancer cell, CAR-T cells bind to it and become activated and become cytotoxic

CAR T cells mediate MHC-unrestricted tumor cell killing by enabling T cells to bind target cell surface antigens through a single-chain variable fragment (scFv) recognition domain.. CAR T cell-mediated lysis of tumor cells will also result in release and cross-presentation of other tumor antigens to endogenous T cells, resulting in a more effective polyclonal anti-tumor response.