Related Experiment Video
Updated: Mar 30, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Phase I trial of EpCAM-targeting immunotoxin MOC31PE, alone and in combination with cyclosporin
Y Andersson1, O Engebraaten1,2,3, S Juell1
1Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0424 Oslo, Norway.
Background:
A phase I trial was performed to determine the maximum tolerated dose (MTD), safety, pharmacokinetics and immunogenicity of the anti-EpCAM immunotoxin (IT) MOC31PE in cancer patients. An important part of the study was to investigate whether the addition of Sandimmune (cyclosporin, CsA) suppressed the development of anti-IT antibodies.
Methods:
Patients with EpCAM-positive metastatic disease were eligible for treatment with intravenous MOC31PE using a modified Fibonacci dose escalation sequence. Maximum tolerated dose was first established without, then with intravenously administered CsA.
Results:
Sixty-three patients were treated with MOC31PE in doses ranging from 0.5 to 8 μg kg(-1). Maximum tolerated dose was 8 μg kg(-1) for MOC31PE alone, and 6.5 μg kg(-1) when combined with CsA. The dose-limiting adverse event was reversible liver toxicity. No radiological complete or partial responses were observed, whereas stable disease was seen in 36% of the patients receiving MOC31PE only. The pharmacokinetic profile of MOC31PE was characterised by linear kinetics and with a half-life of ∼3 h. The addition of CsA delayed the generation of anti-IT antibodies.
Conclusions:
Intravenous infusion of MOC31PE can safely be administered to cancer patients. Immune suppression with CsA delays the development of anti-MOC31PE antibodies. The antitumour effect of MOC31PE warrants further evaluation in EpCAM-positive metastatic disease.
