Chimeric antigen receptors and methods of use

A nucleic acid molecule encoding a chimeric antigen-receptor polypeptide heterodimer comprising a first polypeptide and a second polypeptide, wherein

• a. said first polypeptide comprises an extracellular part of the major histocompatibility complex I (MHC class I) alpha chain, wherein said extracellular part of the MHC alpha chain retains the ability to interact with an oligopeptide and with CD8, and said second polypeptide comprises a β2-microglobulin domain, or
• b. said first polypeptide comprises an extracellular part of the major histocompatibility complex II (MHC class II) alpha chain and said second polypeptide comprises an extracellular part of the major histocompatibility complex II (MHC class II) beta chain, wherein said extracellular parts of the MHC alpha and beta chain retain the ability to interact with an oligopeptide and CD4,
• one of said first polypeptide (a) or (b) and said second polypeptide (a) or (b) further comprises a hinge region, a transmembrane domain and an intracellular domain or intracellular tail of the T cell receptor alpha chain and the other one of said first polypeptide (a) or (b) and said second polypeptide (a) or (b) comprises a hinge region, a transmembrane domain and an intracellular domain of the T cell receptor beta chain.

A chimeric antigen-receptor polypeptide heterodimer comprising a first polypeptide and a second polypeptide, wherein said first polypeptide comprises an extracellular part of the major histocompatibility complex II (MHC class II) alpha chain and said second polypeptide comprises an extracellular part of the major histocompatibility complex II (MHC class II) beta chain;

• wherein the extracellular part of the MHC molecule comprises an MHC class II alpha1 and an MHC class II alpha2 domain forming part of said first polypeptide, and an MHC class II beta1 and an MHC class II beta2 domain forming part of said second polypeptide;
• and
• wherein said first polypeptide and said second polypeptide comprises a hinge region, a transmembrane domain and an intracellular domain of the T cell receptor beta chain.

A chimeric antigen-receptor polypeptide heterodimer comprising a first polypeptide and a second polypeptide, wherein said first polypeptide comprises an extracellular part of the major histocompatibility complex I (MHC class I) alpha chain and said second polypeptide comprises an extracellular part of the major histocompatibility complex I (WIC class I) β2-microglobulin chain;

• wherein the extracellular part of the MHC molecule comprises an MHC class I alpha 1 domain, an MHC class I alpha 2 domain and an MHC class I alpha 3 domain forming part of said first polypeptide;
• and
• wherein said first polypeptide further comprises a hinge region, a transmembrane domain and an intracellular domain or intracellular tail of the T cell receptor alpha chain and said second polypeptide comprises a hinge region, a transmembrane domain and an intracellular domain of the T cell receptor beta chain.