Passive immunotherapy of mice bearing Ehrlich ascites tumor expressing human, membrane-bound placental alkaline phosphatase

Tumour Biol. 2000 May-Jun;21(3):145-52. doi: 10.1159/000030121.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Carcinoma, Ehrlich Tumor / genetics
  • Carcinoma, Ehrlich Tumor / immunology*
  • Carcinoma, Ehrlich Tumor / pathology
  • Carcinoma, Ehrlich Tumor / therapy*
  • Cell Division
  • Cell Membrane / enzymology
  • Cell Transformation, Neoplastic
  • Female
  • Fluorescent Antibody Technique
  • GPI-Linked Proteins
  • Gene Transfer Techniques
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Immunization, Passive*
  • Injections, Intraperitoneal
  • Isoenzymes / genetics*
  • Isoenzymes / immunology*
  • Isoenzymes / metabolism
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Ribonucleoproteins / immunology
  • Survival Rate
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Isoenzymes
  • Ribonucleoproteins
  • Alkaline Phosphatase
  • alkaline phosphatase, placental