CHIMERIC RECEPTOR GENES AND CELLS TRANSFORMED THEREWITH
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.