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

Science. 2008 Aug 15;321(5891):974-7. doi: 10.1126/science.1158545.

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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / adverse effects
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / therapeutic use
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • B-Lymphocytes / immunology
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Lymphocyte Count
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, Follicular / drug therapy*
  • Lymphoma, Follicular / immunology
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / immunology
  • Recurrence
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Bispecific
  • Antineoplastic Agents
  • blinatumomab