RESUMO
Fresenius Biotech GmbH (licensed from TRION Pharma GmbH) is developing catumaxomab, a rat/murine hybrid, trifunctional, bispecific (anti-epithelial cell adhesion molecule and anti-CD3) mAb for the potential intravenous and intraperitoneal treatment of ovarian cancer, gastric cancer, malignant pleural effusion and other cancers, and also for malignant ascites associated with various cancers. In 2007, following the successful completion of a phase II/III clinical trial in patients with malignant ascites from various cancers, Fresenius filed for European approval. Catumaxomab is currently undergoing phase II clinical trials in patients with malignant ascites, ovarian and stomach cancer.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/biossíntese , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/farmacocinética , Ensaios Clínicos como Assunto , Contraindicações , Avaliação Pré-Clínica de Medicamentos , Camundongos , Ratos , Relação Estrutura-AtividadeRESUMO
We have developed a universal DC targeting vehicle that could be a convenient method to deliver any type of antigen to DC. P125, a quadroma (hybrid-hybridoma) secreting bispecific monoclonal antibodies (bsmAb), with one paratope specific for mouse DC DEC-205 and another paratope specific for biotin, was developed by PEG-fusion of the two parental hybridomas and selected by a fluorescence activated cell sorter. The bsmAb were purified using a biotin-Agarose column and the bsmAb activity was demonstrated using ELISA method employing mouse bone marrow DC and biotinylated BSA. Both confocal microscopy and ELISA studies have shown enhanced binding and internalization of biotinylated and FITC-labelled M13 to DC cell in the presence of bsmAb. In vivo studies in mice with biotinylated OVA has shown that in the presence of bsmAb and anti-CD40 mAb, both humoral and cell-mediated responses can be augmented. In addition, only a low concentration of antigen (500 fold less) is required using bsmAb to achieve a similar immune response in mice that were immunized using complete Freund's adjuvant. In the absence of traditional adjuvants, bsmAb targeting of biotinylated antigens to DC could be an alternative, convenient method to deliver antigens to DC. Moreover, this method could be an alternative method to ex vivo stimulation of DC to overcome DC defects and for treatment of cancer.