Most B-cell malignancies express CD19, and a majority of patients with B-cell malignancies are not cured by current standard therapies. Chimeric antigen receptors (CARs) are fusion proteins consisting of antigen recognition moieties and T-cell activation domains. T cells can be genetically modified to express CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was first reported in 2010 after a patient with advanced-stage lymphoma treated at the NCI experienced a partial remission of lymphoma and long-term eradication of normal B cells. Additional patients have subsequently obtained long-term remissions of advanced-stage B-cell malignancies after infusions of anti-CD19 CAR T cells. Long-term eradication of normal CD19+ B cells from patients receiving infusions of anti-CD19 CAR T cells demonstrates the potent antigen-specific activity of these T cells. Some patients treated with anti-CD19 CAR T cells have experienced acute adverse effects, which were associated with increased levels of serum inflammatory cytokines. Although anti-CD19 CAR T cells are at an early stage of development, the potent antigen-specific activity observed in patients suggests that infusions of anti-CD19 CAR T cells might become a standard therapy for some B-cell malignancies.
T cells can be genetically modified to express chimeric antigen receptors (CARs), which are fusion proteins made up of antigen-recognition moieties and T-cell activation domains
CD19 is a suitable target for CAR T cells because it is expressed by B-cell malignancies, but not by normal essential tissues
Depleting endogenous lymphocytes by administering chemotherapy or radiotherapy before infusions of adoptively transferred T cells enhances the in vivo activity of the T cells
Patients have achieved complete remissions during clinical trials of anti-CD19 CAR T cells; however, acute toxicities associated with elevated serum levels of inflammatory cytokines were noted in trials
Evidence for biological activity is provided by long-term depletion of CD19+ normal B cells from several patients receiving infusions of anti-CD19 CAR T cells
Adoptive transfer of anti-CD19 CAR T cells is a potent new form of immunotherapy that has the potential to become an important therapy option for some advanced-stage B-cell malignancies
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This work was supported by intramural funding of the Center for Cancer Research, National Cancer Institute, NIH, USA.
Kite Pharma has signed a Cooperative Research and Development Agreement with the National Cancer Institute (NCI) to support research in the Surgery Branch, NCI, to develop cell transfer therapies involving the genetic engineering of lymphocytes.
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Kochenderfer, J., Rosenberg, S. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 10, 267–276 (2013). https://doi.org/10.1038/nrclinonc.2013.46
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