Method of engineering multi-input signal sensitive T cell for immunotherapy

A method for treating cancer in a patient in need thereof comprising administering to said patient an immune cell comprising a multi-chain chimeric antigen receptor (CAR) comprising:

• an extracellular ligand binding domain capable of recognizing a specific ligand expressed at the surface of a tumor cell, said extracellular ligand binding domain further comprising a hinge selected from CD8β, CD4, CD28, RTK, IgGI, and EpoR2-D2;
• a transmembrane domain;
• an intracellular domain comprising a CD3ζ domain;
• and
• an oxygen-sensitive polypeptide domain,
• wherein said multi-chain CAR comprises part of the alpha, beta, and gamma chains from an Fc receptor comprising an amino acid sequence identity greater than 80% to SEQ ID NO:
• 7, 3 and 4, respectively.