Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma.
Bispecific antibody HEA125 x OKT3 was shown to redirect T lymphocytes toward carcinoma cells and to induce tumor cell lysis in vitro. Preclinical studies have demonstrated that tumor-associated lymphocytes (TAL) derived from malignant ascites can be used as effector cells with a high efficacy and without prior stimulation. These data provided the rationale for a clinical trial to investigate whether bsAb HEA125 x OKT3 is also able to induce tumor cell lysis in vivo and can be used for local treatment of malignant ascites arising from ovarian carcinoma. Ten ovarian carcinoma patients presenting with malignant ascites resistant to chemotherapy were enrolled in the study. They received weekly intraperitoneal injections of 1 mg bsAb diluted in 500 ml NaCl solution to allow homogeneous antibody distribution within the peritoneal cavity. All patients responded clinically well to the therapy. Eight patients experienced a complete and 2 patients a partial reduction of ascites production. A decrease or stabilization of tumor marker CA125 was detected in the sera of 8 patients. Only WHO Grade I and II toxicity was observed including mild fever, chills and allergic eczema. Thus, intraperitoneal application of bsAb HEA125 x OKT3 appears to be an easy and cost effective palliative treatment for ovarian carcinoma with recurrent ascites that leads to a substantially increased quality of life for the patients. During therapy TNF-alpha concentrations raised markedly in the ascites fluid whereas VEGF and sFLT-1 ascites levels declined. This indicates that not only T cell-mediated tumor cell lysis but also changes in vascular permeability due to downregulation of VEGF and its receptors might be responsible for the beneficial therapeutic effect.
Marmé
Alexander
A
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
Strauss
Gudrun
G
Bastert
Gunther
G
Grischke
Eva-Maria
EM
Moldenhauer
Gerhard
G
D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D001201:Ascites / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002455:Cell Division; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D018033:Antibodies, Bispecific