TITLE:
Safety and Therapeutic Efficacy of the Lewis Y Carbohydrate Specific Humanized Antibody MB311 in Patients with Malignant Effusion
AUTHORS:
Thomas Bauernhofer, Helmut Samonigg, Peter Regitnik, Werner Weitzer, Brigitte Lileg, Günter Waxenecker, Susanne Wiederkum, Manuela Kainer, Manfred Schuster, Hans Loibner, Markus Fido, Ralf Kircheis, Andreas Nechansky
KEYWORDS:
Passive Immunotherapy; Therapeutic Antibody; Circulating Tumor Cells; Malignant Effusion; Lewis Y Carbohydrate; Ascites
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.1,
January
6,
2014
ABSTRACT: Purpose: Investigation of safety and tolerability
as well as therapeutic efficacy of the LeY specific humanized mAb MB311 in
cancer pts with malignant effusions in a Phase II clinical
trial. Experimental Design: An openlabel, single treatment arm, uncontrolled
study with MB311 (100 mg per dose,
intravenous infusion on day 1 and 7) in pts with malignant effusion (ascites or
pleural effusion) was conducted with the primary objective to examine safety
and tolerability as well as pharmacokinetics. Secondary objectives were
assessment of pharmacodynamics, volumetric measurement of the malignant
effusion and obtaining data for several immunological parameters. Results: Five
pts (2 pts with gastric cancer
and malignant ascites, 3 pts with
breast cancer and malignant pleural effusion/ascites) have completed the study.
MB311 was well tolerated with only two pts showing the easily manageable side
effects nausea, vomiting (up to grade 2) and one episode
of skin rash (grade 2) after the
first application. Data of 4 pts were
available for evaluating immunologic results and efficacy. In all pts significant
levels of MB311 could be detected in the systemic blood circulation and the
effusion leading to increased infiltration of CD45 positive immune cells (4/5 pts) and resulting in a reduction of tumor cell
counts as detected by immunocytochemistry of effusion samples in 3/5 pts). Most interestingly, the pt with the highest
LeY positive tumor showed a significant reduction of effusion volume after
treatment—this decrease was also evident for Her2/neu positive tumor cells
which were dramatically reduced after MB311 treatment in this breast cancer pt.
Conclusion: MB311 was well tolerated in patients with malignant effusions,
permeated into malignant effusion and attracted immune cells leading to
decreased tumor cell counts in the effusion. In the case of strong LeY expression
of malignant cells in the effusion a pronounced decrease in LeY, EpCAM and
Her2/neu positive tumor cells and a significant reduction of the effusion
volume could be demonstrated.