Chimeric Antigen Receptor (CAR) T-cell therapy is being used with a large number of malignancies. Unfortunately, it may have a number of serious adverse effects. One of these is referred to as "on target, off tumor" toxicity.
Mechanism: With CAR therapyT-cells attack tumors through receptors that recognize tumor antigen. If normal tissues bear the same or similar antigen then the normal tissue may be destroyed as well.
Normal Tissue
Consequence
colon
colitis
B cells
B cell lymphopenia with immunodeficiency
lungs
pneumonitis
biliary tract
cholangitis with cholestasis
multiple organs
multi-organ failure
The diagnosis requires exclusion of alternative diagnoses.
The diagnosis is supported if a shared antigen can be demonstrated between the normal tissue and tumor.
Risk factors for on target, off tumor toxicity:
(1) high dose of infused CART cells
(2) nonspecific target antigen
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