Concepedia

Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody

Ralf C. Bargou, Eugen Leo, Gerhard Zugmaier, Matthias Klinger, Mariele Goebeler, Stefan Knop, Richard Noppeney, Andreas Viardot, Martin Schüler, Hermann Einsele,

Science · 2008 · 1.1K citations · 24 references

DOI

TL;DR

Previous attempts have shown the potential of T cells in immunotherapy of cancer. The study reports the clinical activity of blinatumomab, a bispecific antibody designed to engage all cytotoxic T cells for cancer cell lysis. Blinatumomab functions by engaging cytotoxic T cells to mediate lysis of cancer cells. Doses as low as 0.005 mg/m²/day eliminated circulating target cells, while 0.015 mg/m² induced partial or complete regressions and 0.06 mg/m² achieved regression in all seven patients, with additional clearance from bone marrow and liver, indicating therapeutic potential.

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.