Chimeric antigen receptors with an optimized hinge region

A protein comprising

• (i) a signal peptide;
• (ii) a target specific recognition domain;
• (iii) a linker region, connecting domain (ii) and domain (iv),
• wherein the linker region does not contain cysteine residue(s) and is selected from the following:
• the amino acid sequence of SEQ ID NO. 2,
• an amino acid sequence with at least 95% sequence identity to SEQ ID NO. 2 under the proviso that amino acid residue 48 is not a cysteine and is a serine, and
• an amino acid sequence that differs in one, two or three amino acid residues from the amino acid sequence of SEQ ID NO. 2 under the proviso that amino acid residue 48 is not a cysteine and is a serine;
• and
• (iv) an effector domain comprising a transmembrane region and one or more intracellular signaling domains,
• wherein the effector domain (iv) comprises, or is, a fusion of a fragment of a human costimulatory receptor fused to a fragment of a zeta-chain of a human CD3 complex of a T-cell receptor.