CAR T-Cell Therapy

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

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II. 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

III. Medications: CD19 Cell Surface Targets

  1. Tisagenlecleucel
    1. B Cell Acute Lymphoblastic Leukemia
  2. Axicabtagene ciloleucel
    1. B Cell Lymphoma subtypes

IV. 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

V. 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

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