Tumor regression in cancer patients by very low doses of a T cell-engaging antibody.
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.
Bargou
Ralf
R
Interdisciplinary Phase I/II Unit of the University of Würzburg, Klinikstrasse 6-8, 97070 Würzburg, Germany.
Leo
Eugen
E
Zugmaier
Gerhard
G
Klinger
Matthias
M
Goebeler
Mariele
M
Knop
Stefan
S
Noppeney
Richard
R
Viardot
Andreas
A
Hess
Georg
G
Schuler
Martin
M
Einsele
Hermann
H
Brandl
Christian
C
Wolf
Andreas
A
Kirchinger
Petra
P
Klappers
Petra
P
Schmidt
Margit
M
Riethmüller
Gert
G
Reinhardt
Carsten
C
Baeuerle
Patrick A
PA
Kufer
Peter
P
D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology; D018655:Lymphocyte Count; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000276:immunology; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; C510808:blinatumomab