Chimeric receptor genes and cells transformed therewith

Abstract

Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.

1 - 41 . (canceled) 
     
     
         42 . An adoptive immunotherapeutic method of treating a patient having a condition, comprising administering to the patient cells that have been transformed with a chimeric gene, the chimeric gene containing
 a) a first DNA segment encoding a single-chain Fv (scFv) domain of an antibody and   b) a second DNA segment encoding a lymphocyte-activating molecule to express the scFv domain and the lymphocyte-activating molecule on the surface of the lymphocytes and to provide antibody specificity, wherein the second DNA segment of the chimeric gene encodes:   i) a lymphocyte receptor chain;   ii) a polypeptide of the TCR/CD3 complex;   iii) a receptor molecule which transduces a costimulatory signal for lymphocyte activation; or   iv) a subunit of an IL-2 receptor.   
     
     
         43 . The method of  claim 42 , wherein the second DNA segment of the chimeric gene encodes a polypeptide of the TCR/CD3 complex and the polypeptide of the TCR/CD3 complex is selected from the group of polypeptides consisting of the zeta chain and the eta isoform chain. 
     
     
         44 . The method of  claim 42 , wherein the second DNA segment of the chimeric gene encodes a receptor molecule which transduces a costimulatory signal for lymphocyte activation and the costimulatory receptor molecule is a CD2 or CD28 receptor molecule. 
     
     
         45 . The method of  claim 42 , wherein the second DNA segment of the chimeric gene encodes a subunit of an IL-2 receptor and the subunit is a a or B subunit of an IL-2 receptor. 
     
     
         46 . The method of  claim 42 , wherein the antibody is directed against a tumor-specific antigen. 
     
     
         47 . The method according to  claim 46  wherein the tumor-specific antigen is a gastric cancer antigen. 
     
     
         48 . The method according to  claim 46  wherein the tumor-specific antigen is a breast cancer antigen. 
     
     
         49 . The method of  claim 46 , wherein the tumor-specific antigen is Neu/HER2. 
     
     
         50 . The method according to  claim 46 , wherein the antibody is an anti-HER2 antibody. 
     
     
         51 . The method according to  claim 48 , wherein the anti-HER2 antibody is mAb N29. 
     
     
         52 . The method according to  claim 46  wherein the tumor-specific antigen is an ovarian cancer antigen. 
     
     
         53 . The method according to  claim 42 , wherein the cells are circulating lymphocytes. 
     
     
         54 . The method according to  claim 53 , wherein the cells are primary T cells. 
     
     
         55 . An adoptive immunotherapeutic method of treating a patient having a condition, comprising administering to the patient cells that have been transformed with a chimeric gene, the chimeric gene containing
 a) a first DNA segment encoding a single-chain Fv (scFv) domain of an antibody and   b) a second DNA segment encoding a lymphocyte-activating molecule to express the scFv domain and the lymphocyte-activating molecule on the surface of the lymphocytes and to provide antibody specificity, wherein the first DNA segment of the chimeric gene encodes an scFv domain directed against virus-infected cells.   
     
     
         56 . An adoptive immunotherapeutic method of treating a patient having a condition, comprising administering to the patient cells that have been transformed with a chimeric gene, the chimeric gene containing a) a first DNA segment encoding a single-chain Fv (scFv) domain of an antibody and b) a second DNA segment encoding a lymphocyte-activating molecule to express the scFv domain and the lymphocyte-activating molecule on the surface of the lymphocytes and to provide antibody specificity, wherein the antibody is an anti-IgE antibody. 
     
     
         57 . The method of  claim 56 , wherein the scFv is scFvCβ.