Chimeric antigen receptor specific for tumor cells

Abstract

The present invention is directed to ligand like a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for one or more antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8; cell populations expressing such CARs and the use of the cell populations for cancer therapy.

1 ) A ligand, comprising an antigen binding domain specific for one or more antigens characterized in that the ligand is a chimeric antigen receptor (CAR), comprising an anti tag binding region which binds to a tag which is coupled to an antigen binding domain specific for one or more antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8. 
     
     
         2 ) A ligand according to  claim 1 , characterized in that the tag is Biotin, a hapten, FITC or other fluorochrome molecules, FLAG, HIS, YOL MYC, Dextran, FcR, antibody-isotypes, artificially engineered epitopes, FAB or FAB2 binders. 
     
     
         3 ) A ligand according to  claim 1 , characterized in that the ligand comprises at least two different antigen binding domains specific for at least two different antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8. 
     
     
         4 ) A ligand according to  claim 1 , characterized in that the CAR comprises an antigen binding domain specific for CLA in combination with one or more antigens selected from the group consisting of CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8. 
     
     
         5 ) A ligand according to  claim 1 , characterized in that the CAR comprises an antigen binding domain, an transmembrane domain and/or an intracellular signaling domain and comprising at least two antigen binding domains specific for two different antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8 are conjugated to the same or a different transmembrane domain and/or intracellular signaling domain. 
     
     
         6 ) A ligand according to  claim 1 , characterized in that the transmembrane domain comprises a sequence of the transmembrane domains of 4-1BB, CD8 and/or CD28; and the intracellular signaling domain comprises a sequence of the intracellular signaling domains of one or more of CD28, CD137 and CD3zeta. 
     
     
         7 ) A ligand according to  claim 1 , characterized in that the ligand is an engineered cell expressing at least one antigen binding domain specific for one or more antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8. 
     
     
         8 ) A method of binding a cancer cell with a ligand according to  claim 1 . 
     
     
         9 ) A method of binding a cancer cell according to  claim 8  characterized in that the ligand comprises at least two different antigen binding domains specific for at least two different antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8. 
     
     
         10 ) A population of engineered cells expressing at least one ligand according to  claim 1 . 
     
     
         11 ) Use of the population of engineered cells according to  claim 10  for treatment of human cancer. 
     
     
         12 ) A pharmaceutical composition comprising a population of engineered cells expressing a CAR according to  claim 1 . 
     
     
         13 ) Use of the pharmaceutical composition according to  claim 12  for treatment of human cancer. 
     
     
         14 ) Use of the pharmaceutical composition according to  claim 12  in combination with a chemotherapeutic, radiation, or immunomodulatory agent for treatment of cancer.