Although CD19 has proved to be an attractive and effective target for chimeric antigen receptor (CAR) T-cell therapies in hematologic malignancies, a significant subset of patients treated with this groundbreaking form of immunotherapy eventually relapse, with some developing a more aggressive and harder-to-treat form of their disease.1-3
. Meanwhile, at least 2 dozen other trials are ongoing in China and Europe, according to clinicaltrials.gov.
CD19 Targeting Makes Impact
CAR T cells are a form of adoptive cell therapy in which the effector cells of the immune system are transplanted into a patient to boost the antitumor immune response. The T cells are genetically engineered outside the body to express a CAR that is designed to target a TAA. CARs are artificial T-cell receptors (TCRs) made of the single-chain variable fragment from an anti- body, which confers antigen specificity, fused to an intracellular portion composed of the CD3ζ chain of the TCR and 1 or more costimulatory domains, which trigger T-cell activation. In this way, an antibody-like sensitivity is essentially grafted onto a T cell.7,8
Figure. CAR T Cells in Signaling Network4
BCR indicates B-cell receptor; CAR, chimeric antigen receptor; CCR4, CC chemokine receptor 4. CAR-modified T cells targeting CD19 and CD22 transmembrane proteins on a malignant B cell. T-cell activation leads to apoptosis of the cancer cell.
Last year marked the first FDA approvals of this type of immunotherapy. These approvals and much of the research conducted to date have focused on targeting the TAA CD19—an ideal target for the treatment of leukemia and lymphoma thanks to its restriction to B cells and its frequent expression in B-cell malignancies.
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