Treatment of hematological malignancies with T cell redirected bispecific antibodies: current status and future needs

Expert Opin Biol Ther. 2019 Jul;19(7):707-720. doi: 10.1080/14712598.2019.1604672. Epub 2019 May 13.

Abstract

Introduction: Enthusiasm for developing therapeutic bispecific antibodies (BsAbs) for cancer applications has become intense in the past decade facilitated by advances in molecular biology, hybridoma technology, and protein engineering. The central strategy in BsAb engineering is to combine the specificities directed at effector cells, and at a tumor target associated antigen (TAA) into a single construct.

Areas covered: This article highlights the clinical use of BsAbs to target effector cells to multiple myeloma (MM), non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). We discuss the successes, challenges, and future strategies. Secondary literature search was performed using Pubmed, clinicaltrials.gov and non-proprietary internet search engines.

Expert opinion: The use of BsAb constructs to target hematologic malignancies has achieved limited success to date. There continues to be a high level of enthusiasm for developing and applying new constructs to overcome the challenges in engineering and clinical application for hematologic malignancies.

Keywords: ALL; AML; Bispecific; Multiple myeloma; NHL; antibody; hematologic; malignancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Bispecific / therapeutic use*
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / immunology
  • Humans
  • Immunotherapy
  • Interleukin-3 Receptor alpha Subunit / immunology
  • Leukemia, Myeloid, Acute / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Sialic Acid Binding Ig-like Lectin 3 / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Bispecific
  • Interleukin-3 Receptor alpha Subunit
  • Sialic Acid Binding Ig-like Lectin 3
  • blinatumomab