Phase I Dose Escalation Study with the Lewis Y Carbohydrate Specific Humanized Antibody IGN311

Abstract

Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with

Safety and Therapeutic Efficacy of the Lewis Y Carbohydrate Specific Humanized Antibody MB311 in Patients with Malignant Effusion

“…Regarding MB311 (which was applied intravenously) the reduction of the effusion volume which were strongly positive for LeY at week 1 is in accordance with our previous data showing the eradication of disseminated tumor cells in the blood of two pts with high LeY expression of their primary tumor [28]. Regarding the anti-tumor activity of MB311 effector mechanisms, CDC and ADCC have been demonstrated against LeY positive tumor cells in ex vivo studies [28]. Furthermore, MB311 has been also shown to block signal transduction through LeY glycosylated growth factor receptors such as EGFR and Her2-neu on tumor cells as demonstrated in cell culture and in in vivo studies [24,30].…”

“…Catumaxomab is a bispecfic (EpCAM/CD3) mAb that is approved in Europe for the intraperitoneal treatment of patients with ascites originating from epithelial tumors. Regarding MB311 (which was applied intravenously) the reduction of the effusion volume which were strongly positive for LeY at week 1 is in accordance with our previous data showing the eradication of disseminated tumor cells in the blood of two pts with high LeY expression of their primary tumor [28]. Regarding the anti-tumor activity of MB311 effector mechanisms, CDC and ADCC have been demonstrated against LeY positive tumor cells in ex vivo studies [28].…”

“…Intravenous application of MB311 in this study enabled the patients' serum to lyse tumor cells by two mechanisms, Complement Dependent Cytotoxicity (CDC) and Antibody Dependent Cellular Cytotoxicity (ADCC). Moreover, disseminated tumor cells detectable in two patients before treatment were eliminated after treatment with MB311 [28]. In animal models, MB311 was also shown to block signal transduction through LeY glycosylated growth factor receptors such as EGFR and Her2-neu on tumor cells [24,30].…”

“…For another humanized anti-LeY mAb, IGN311 (now renamed to MB311), a Phase I dose escalation study was recently conducted and safety, tolerability, pharmacokinetic data, anti-tumor activity and immunologic parameters were assessed [28,29]. Intravenous application of MB311 in this study enabled the patients' serum to lyse tumor cells by two mechanisms, Complement Dependent Cytotoxicity (CDC) and Antibody Dependent Cellular Cytotoxicity (ADCC).…”

Induction of Human Anti-Human Antibody Responses (Ab2) after Application of a Humanized Lewis Y Carbohydrate Specific Antibody (Ab1): Connection of Prolonged Disease Stabilization with Ab3 Induction?

“…To determine safety, tolerability, pharmacokinetics, and antitumor activity of IGN311, a clinical Phase I study with twelve patients with LeY positive tumors was performed [14]. After two IGN311 infusions (at days 1 and 15), 50% of the patients developed a HAHA response as determined by a surface plasmon resonance (SPR) based assay [15].…”