Cellular and humoral responses after multiple injections of unconjugated chimeric monoclonal antibody MOv18 in ovarian cancer patients: a pilot study

• Published in: Journal of cancer research and clinical oncology 2002-09, Vol.128 (9), p.484-492
• Main Authors: VAN ZANTEN-PRZYBYSZ, Iwona, MOLTHOFF, Carla, GEBBINCK, Jacqueline Klein, VON MENSDORFF-POUILLY, Silvia, VERSTRAETEN, Rob, KENEMANS, Peter, VERHEIJEN, René
• Format: Article
• Language: English
• Subjects: Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm - therapeutic use; Antibody-Dependent Cell Cytotoxicity - drug effects; Antineoplastic agents; Biological and medical sciences; CD4-CD8 Ratio; Female; Humans; Immunity, Cellular - drug effects; Immunology; Immunophenotyping; Immunotherapy; Injections; Injections, Intravenous; Lymphocyte Activation - drug effects; Medical sciences; Middle Aged; Oncology; Ovarian cancer; Ovarian Neoplasms - immunology; Ovarian Neoplasms - therapy; Pharmacology. Drug treatments; Pilot Projects; Recombinant Fusion Proteins - therapeutic use; Toxicity; Treatment Outcome
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-002-0348-z

Chimeric antibody MOv18 (c-MOv18) mediates antibody-dependent cellular cytotoxicity (ADCC) in vitro. To study the toxicity of c-MOv18 and its immunological effects, five ovarian cancer patients received intravenous injections for 4 weeks. ADCC activity of c-MOv18 was tested in a (51)Cr-release assay using IGROV1 and KB cells. Patients' peripheral blood mononuclear cells (PBMC) were phenotyped for CD3, CD4, CD8, and CD25 by FACS analysis and tested for T-cell proliferation in vitro in the presence of c-MOv18 with and without IL-2. Toxicity was mild and transient. No human anti-chimeric antibodies were found. Increased ADCC levels corresponding with a slight increase in CD4+ and CD8+ fractions were observed after the first injection, while the CD4/CD8 ratio and the levels of CD25 remained unchanged. c-MOv18 did not have a mitogenic effect on patients' PBMC and adding IL-2 did not change the degree of proliferation. In three patients stable disease was achieved for up to 4 months, 9 months and 14 months, respectively. Immunotherapy aiming at the patient's immunological capacity has minor effects in ovarian cancer patients that have been heavily pretreated with chemotherapy. Such strategies should be evaluated in patients who are more immunocompetent, i.e., before excessive chemotherapy and after achieving microscopic or small volume disease.