Lysis of small cell carcinoma of the lung (SCCL) cells by cytokine-activated monocytes and natural killer cells in the presence of bispecific immunoconjugates containing a gastrin-releasing peptide (GRP) analog or a GRP antagonist.
Lung cancer remains the leading cause of cancer deaths in the United States. We have developed a new immunotherapeutic approach to the treatment of small cell carcinoma of the lung (SCCL) by targeting the gastrin-releasing peptide receptor (GRP-R) expressed on the surface of these cells. Bispecific immunoconjugates were constructed by chemical fusion of a GRP analog or a GRP antagonist with monoclonal antibodies directed to the cytotoxic trigger molecules Fc gamma RI and Fc gamma RIII on various immune effector cells. We demonstrated that these bispecific immunoconjugates bound to target SCCL cells in a dose-dependent manner. In the presence of these immunoconjugates, more than 80% of SCCL cells were lysed by cytokine-activated monocytes and natural killer (NK) cells measured by a 51Cr-release assay. These data indicate that bifunctional antibodies targeting GRP may have clinical use.
Chen
J
J
Division of Hematology/Bone Marrow Transplantation, University of Pittsburgh Medical Center, PA 15213, USA.
Zhou
J H
JH
Mokotoff
M
M
Fanger
M W
MW
Ball
E D
ED
D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000473:pathology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D019886:Gastrin-Releasing Peptide; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009363:Neoplasm Proteins / Q000187:drug effects*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D018004:Receptors, Bombesin / Q000187:drug effects*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D018033:Antibodies, Bispecific; D018796:Immunoconjugates; D009363:Neoplasm Proteins; D010455:Peptides; D018004:Receptors, Bombesin; D017452:Receptors, IgG; D011994:Recombinant Proteins; D019886:Gastrin-Releasing Peptide; D007371:Interferon-gamma