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CAR T-Cell Therapy

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CAR T-Cell Therapy, CAR T Cell Therapy, Chimeric Antigen Receptor T Cell Therapy, Tisagenlecleucel, Axicabtagene ciloleucel

  • Mechanism
  1. Extraction of WBCs via Leukapheresis
    1. White Blood Cells (including T Cells) extracted from patient's blood and T Cells are concentrated
    2. White cells of interest for re-engineering
      1. Natural Killer Cells (NK cells)
      2. Lymphokine-activated Killer T Cells
      3. Cytotoxic T cells
      4. Dendritic cells
  2. Reprogramming
    1. Synthesis of Gene encoding for chimeric Antigen receptor (CAR) that targets specific Antigen (along with cosignals)
    2. Manufacturing introduces into the T Cells, a CAR-encoded gene via viral vector
  3. Multiplication
    1. Engineered CAR T Cells are multiplied in a bioreactor
  4. Preparation with lymphodepletion
    1. Patient is administered Chemotherapy to suppress their own White Blood Cells
  5. Treatment
    1. Engineered CAR T Cells are infused into the patient
    2. T Cells recognize target Antigens and destroy cancer cells
      1. Sensitization to additional cancer cell components (cross-prime), providing additional cancer destruction
  • Preparations
  • CD19 Cell Surface Targets
  1. Tisagenlecleucel
    1. B Cell Acute Lymphoblastic Leukemia
  2. Axicabtagene ciloleucel
    1. B Cell Lymphoma subtypes
  • Adverse Effects
  1. See Cytokine Release Syndrome (CRS)
  2. Neurotoxicity
    1. Signs
      1. Headache
      2. Expressive Aphasia
      3. Confusion to Delirium
      4. Seziures (including nonconvulsive Status Epilepticus in 10% of cases)
      5. Cerebral edema
      6. Encephalopathy (CAR T Cell-related encephalopathy or CRES)
    2. Management
      1. Seizure Prophylaxis
      2. Corticosteroids may be more effective than Tocilizumab (see dosing under CRS as above)
  3. On-Target/Off Tumor Recognition
    1. T Cell attacks noncancerous cells displaying target Antigen
  • References
  1. Jansson and Pallin (2020) Crit Dec Emerg Med 34(4): 19-28
  2. Santomasso (2019) Am Soc Clin Oncol Educ Book 39:433-444