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The TIL therapy carries a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment

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Subtle dynamics allows the C-terminal of the ligand to access the ECD binding site, and the binding of the ligand triggers further dissociation between the ECD and TMD, allowing the N-terminal to enter the orthosteric pocket in the TMD and activate the receptor