Passive immunotherapy of mice bearing Ehrlich ascites tumor expressing human, membrane-bound placental alkaline phosphatase.
The objective of our study was to test if a tumor expressing a transgene coding for a membrane-bound protein is amenable to immunotherapy by antibodies to the same protein. To this end, we have established an Ehrlich ascites tumor (EAT) cell line, EAT-DAP, stably expressing human, membrane-bound placental alkaline phosphatase (PLAP) by infecting EAT cells (EATC) with the retroviral vector DAP and selecting neomycin-resistant cells. EATC and EAT-DAP cells grew at similar rates in vitro, and produced ascites tumor in Swiss-Webster mice with similar efficiency. We have treated mice bearing EAT-DAP ascites tumor with a mouse monoclonal antibody to human PLAP or with a monoclonal antibody to human C proteins of the heterogenous ribonucleoprotein complex (hnRNP). The average survival of mice treated with anti-hnRNP was 16.4 +/- 1.1 days (n = 8). Treatment with anti-PLAP prolonged the survival of mice; in 4 mice average survival was 23.3 +/- 5.7 days. Four animals, however, survived for 60 days when they were killed and had no visible signs of tumor. These data support the notion that passive immunotherapy using antibodies against a membrane protein, expressed in tumor cells transduced by a viral vector coding for that protein, may be effective in controlling tumor growth.
Barka
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Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, NY 10029, USA. Tibor.Barka@mssm.edu
Henderson
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van der Noen
H M
HM
D000469:Alkaline Phosphatase; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D002462:Cell Membrane / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D005260:Female; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins; D018014:Gene Transfer Techniques; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012261:Ribonucleoproteins / Q000276:immunology; D015996:Survival Rate; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007527:Isoenzymes; D012261:Ribonucleoproteins; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental