Pharm

CAR T-Cell Therapy

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

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
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
Multiplication
1. Engineered CAR T Cells are multiplied in a bioreactor
Preparation with lymphodepletion
1. Patient is administered Chemotherapy to suppress their own White Blood Cells
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

See Cytokine Release Syndrome (CRS)
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)
On-Target/Off Tumor Recognition
1. T Cell attacks noncancerous cells displaying target Antigen