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PMID: 18703743 Published · ppublish English Clinical Trial, Phase I Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Tumor regression in cancer patients by very low doses of a T cell-engaging antibody.

Science (New York, N.Y.) ·Vol. 321 ·No. 5891 ·2008-08-15 ·Pages 974-7

Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M, Einsele H, Brandl C, Wolf A, Kirchinger P, Klappers P, Schmidt M, Riethmüller G, Reinhardt C, Baeuerle PA, Kufer P

Abstract

Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non-Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell-engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.

MeSH Terms
Antibodies, Bispecific/administration & dosage,adverse effects,immunology,therapeutic use Antineoplastic Agents/administration & dosage,adverse effects,therapeutic use B-Lymphocytes/immunology Humans Immunologic Memory Immunophenotyping Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy,immunology Lymphocyte Count Lymphoma, B-Cell/drug therapy,immunology Lymphoma, Follicular/drug therapy,immunology Lymphoma, Mantle-Cell/drug therapy,immunology Recurrence T-Lymphocytes/immunology T-Lymphocytes, Cytotoxic/immunology
Chemicals
Antibodies, Bispecific Antineoplastic Agents blinatumomab
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Bargou Ralf
Interdisciplinary Phase I/II Unit of the University of Würzburg, Klinikstrasse 6-8, 97070 Würzburg, Germany.
Leo Eugen
Zugmaier Gerhard
Klinger Matthias
Goebeler Mariele
Knop Stefan
Noppeney Richard
Viardot Andreas
Hess Georg
Schuler Martin
Einsele Hermann
Brandl Christian
Wolf Andreas
Kirchinger Petra
Klappers Petra
Schmidt Margit
Riethmüller Gert
Reinhardt Carsten
Baeuerle Patrick A
Kufer Peter
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2008-08-15
Pages
974-7
Language
English
Region
United States
NLM ID
0404511
Subset
IM
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