Targeting of T cells to CEA-expressing tumor cells by chimeric immune receptors with a highly specific single-chain anti-CEA activity.
BACKGROUND
Lymphokine-activated killer (LAK) cell therapy or cytokine gene therapy is a potential new modality in the treatment of cancer. However, one limitation in the use of adoptive cellular immunotherapy for cancer lies in the difficulty in obtaining tumor-specific effector cells which can efficiently reach their target cells.


METHODS
To effectively target T cells to carcinoembryonic antigen (CEA)-positive tumor cells, we constructed a chimeric immune receptor (CIR) gene which encoded a highly specific anti-CEA scFv antibody, the human CD8 alpha hinge region, the CD28 transmembrane and cytoplasmic domains, and the human CD3 zeta-chain. The resulting CIR gene, termed F39scFv/CIR-2, was transfected into human T cells.


RESULTS
The cell surface expression of the F39scFv/CIR-2 receptors in T cells was demonstrated by flow cytometry. When incubated with CEA-positive tumor cells, the transfected T cells formed rosette-like aggregates around the tumor cells, thus indicating the cell-specific targeting of T cells.


CONCLUSIONS
This strategy may allow the development of new approaches for the adoptive immunotherapy of CEA-positive tumors in humans, especially in combination with LAK cell therapy or cytokine gene therapy.
Arakawa
Fumiko
F
Department of Biochemistry, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
Shibaguchi
Hirotomo
H
Xu
Zhongwei
Z
Kuroki
Masahide
M
D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D018106:CD28 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D016827:CD8 Antigens; C431698:CD8alpha antigen; D002272:Carcinoembryonic Antigen; D007128:Immunoglobulin Fragments; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins