Cereblon-based heterodimerizable chimeric antigen receptors

A CAR comprising (a) a first polypeptide comprising an antigen-binding domain, a transmembrane domain, cereblon or a functional portion thereof, wherein said cereblon or a functional portion thereof is capable of binding to a cereblon-binding compound, and a polypeptide comprising a primary cell signaling domain, wherein said first polypeptide does not comprise a costimulatory domain;

• and (b) a second polypeptide comprising a transmembrane domain, Aiolos or a functional portion thereof or Ikaros or a functional portion thereof, wherein said Aiolos or a functional portion thereof or Ikaros or a functional portion thereof is capable of binding a cereblon-binding compound, and a costimulatory domain;
• wherein in the presence of said cereblon-binding compound, said first polypeptide and said second polypeptide form a heterodimer.

The CAR of claim 17, wherein said antibody is a single chain Fv fragment (scFv).

A dimerizable artificial cell death receptor comprising (a) a first polypeptide comprising an apoptosis-inducing domain and cereblon or a functional portion thereof, wherein said cereblon or a functional portion thereof is capable of binding to a cereblon-binding compound, and (b) a second polypeptide comprising an apoptosis-inducing domain and Aiolos or a functional portion thereof or Ikaros or a functional portion thereof, wherein said Aiolos or a functional portion thereof or Ikaros or a functional portion thereof is capable of binding to a cereblon-binding compound;

• wherein said first polypeptide and said second polypeptide dimerize in the presence of said cereblon-binding compound to generate an apoptosis-inducing signal.