Antibodies against the MUC1-C/extracellular domain (MUC1-C/ECD)
The present invention is directed to antibodies binding to MUC1-C/extracellular domain (MUC1-C/ECD) and methods of using such antibodies to treat cancers that express the MUC1 antigen.
1. A chimeric antigen receptor (CAR) comprising:
(i) an ectodomain comprising single chain antibody variable region that binds selectively to MUC1-C/extracellular domain (MUC1-C/ECD) defined by SEQ ID NO: 2, wherein said single chain antibody comprises a variable heavy chain comprising CDR1, CDR2 and CDR3 regions comprising SEQ ID NOS: 76, 77 and 78, respectively, and a variable light chain comprising CDR1, CDR2 and CDR3 regions comprising SEQ ID NOS: 79, 80 and 81, respectively, with a flexible hinge attached at the C-terminus of said single chain antibody variable region;
(ii) a transmembrane domain; and
(iii) an endodomain,
wherein said endodomain comprises a signal transduction function when said single-chain antibody variable region is engaged with MUC1.
2. The (CAR) of claim 1 , wherein said transmembrane and endodomains are derived from the same molecule.
3. The (CAR) of claim 1 , where said endodomain comprises a CD3-zeta domain or a high affinity FcεRI.
4. The (CAR) of claim 1 , wherein the flexible hinge is from CD8α or Ig.