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CAR T-Cell Therapy: FDA Approves ‘Living Drugs’ for Cancer Treatment in Children and Adults


  • ‘CAR’ (chimeric antigen receptor) refers to the synthetic receptors that are genetically engineered and integrated into the T-cell surface
  • CAR T-cell therapy is a type of adoptive cell transfer (ACT) where a patient’s cells are removed, genetically engineered to attack her cancer cells and then returned back to the patient


  • The genetically engineered CAR is not an antibody found in nature but rather is a synthetic construct that is made up of various fragments and domains
    • T-cells from a patient with cancer are engineered to produce these CAR T-cells, outfitted with synthetic antibodies specific to the target cancer cell antigen, which are then infused back into the patient
    • Scientists choose domains that will maximize recognition of the target antigen on the tumor cell
  • Domains within the cell are also important and designed to affect cell function
  • Continuing research has led to improvements in
    • Expansion (ability of CAR T-cells to multiply after infusion into the patient)
    • Persistence (survival after infusion into the patient)
    • Production time (from weeks to days)


Pediatric Oncology

  • FDA (August 2017) approved the first CAR T-cell therapy, tisagenlecleucel, for children with acute lymphoblastic leukemia (ALL) who have relapsed at least twice or who have not responded to standard therapy
    • The synthetic antibodies target the CD19 antigen found only on B-cells
    • The CAR T-cells undergo expansion in the laboratory, are infused back into the patient following lymphodepletion and then will undergo expansion again
    • Many of the children in the tisagenlecleucel trials have had complete long lasting remissions
      • Previously, no known treatment available
    • The FDA granted tisagenlecleucel Priority Review and Breakthrough Therapy designations

Adult Oncology

  • FDA (October 2017) approved the first drug for adults, axicabtagene ciloleucel, for the treatment of an aggressive type of non-Hodgkin lymphoma
    • This CAR T-cell therapy targets CD19 cells and is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma
  • Individuals with DLBCL will go into remission after treatment but approximately a third either don’t respond or relapse and on average will survive only 6 months
  • In a drug trial that included 101 patients, 36% went in to remission and in 82%, the tumor shrank by ≥ 50%
  • Known risks were seen in the trial, including brain toxicity

Examples of ACT: TCR T-cells and CAR T-cells (tap to enlarge)


Credit: National Cancer Institute


  • Other examples of ACT beyond CAR T
    • Tumor-Infiltrating Lymphocytes (TILs): Immune cells that can penetrate tissues around the tumor based on cancer mutation recognition
      • Currently being studied in colorectal and liver cancer
    • T-cell Receptors (TCRs): As opposed to CAR T approach, TCRs use naturally receptors that recognize antigens within tumor cells
      • Currently being studied in melanoma and sarcoma
  • CAR T-cell therapy side effects include
    • Cytokine-release syndrome (CRS) that results from rapid and massive release of cytokines into the bloodstream resulting in fevers and hypotension
      • Indicates T-cells are working
      • CRS manageable with supportive therapies
    • B-cell aplasia, where B-cells, including normal cells, are killed off by the CAR T-cell therapy
      • Treatment includes immunoglobin therapy to fight dangerous infection
    • Cerebral edema noted in some trials but not others
    • Neurotoxicity (confusion or seizure-like activity) which is short lived and reversible


FDA News Release:  FDA approval brings first gene therapy to the United States 

CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers

Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment

Driving CAR T-cells forward

FDA Approved Drugs: YESCARTA (axicabtagene ciloleucel)

FDA Approved Drugs: KYMRIAH (tisagenlecleucel)