Antibody-Targeted Chemotherapy with the Calicheamicin Conjugate hu3S193- N -Acetyl γ Calicheamicin Dimethyl Hydrazide Targets Lewisy and Eliminates Lewisy-Positive Human Carcinoma Cells and Xenografts

Abstract

ABSTRACT

A Phase I Biodistribution and Pharmacokinetic Trial of Humanized Monoclonal Antibody Hu3s193 in Patients with Advanced Epithelial Cancers that Express the Lewis-Y Antigen

“…The favorable pharmacokinetics of hu3S193 and high tumor concentrations achieved at the dose levels studied in this trial support the use of hu3S193 for immune therapy of solid tumors, alone or in combination with other treatments. Hu3S193 has also been shown to have improved efficacy when radiolabeled and combined with chemotherapy or linked to a drug in preclinical models (25,26,28). Collectively, these results, therefore, indicate the potential for hu3S193 treatment of metastatic Le y -expressing cancers, and further phase I/II trials aimed at optimizing dosage and scheduling of hu3S193 are ongoing.…”

Phase I Biodistribution and Pharmacokinetic Study of Lewis Y–Targeting Immunoconjugate CMD-193 in Patients with Advanced Epithelial Cancers

“…Hu3S193 is currently under development in phase II trials as a naked humanized antibody in Le y -expressing tumors. Dosedependent regression of Le y -expressing human carcinoma xenografts by the immunoconjugate CMD-193 has been shown in preclinical studies, highlighting the potential therapeutic potential of CMD-193 in cancer patients (15). Initial clinical development of CMD-193 involved a dose escalation phase I study in patients with Le y -expressing advanced solid tumors with an expanded preliminary evaluation of efficacy in patients with nonsmall cell lung carcinoma.…”

Radioimmunotherapy with α-Particle–Emitting 213Bi-C-Functionalized trans-Cyclohexyl-Diethylenetriaminepentaacetic Acid-Humanized 3S193 Is Enhanced by Combination with Paclitaxel Chemotherapy

“…The humanized anti-Le y mAb humanized 3S193 (hu3S193) is currently under investigation in phase I/II trials in patients with Le y -positive tumors. The specificity of hu3S193 for Le y makes this mAb an attractive candidate for immunotherapy as well as the targeted delivery of cytotoxics, such as radioisotopes, to tumor cells (2). Accordingly, the biodistribution and antitumor efficacy of radiolabeled hu3S193 have been investigated in preclinical tumor xenograft animal studies of radioimmunotherapy (3,4).…”