Antibody-drug conjugates in hematologic malignancies

Am Soc Clin Oncol Educ Book. 2013. doi: 10.14694/EdBook_AM.2013.33.e108.

Abstract

Antibody-drug conjugates (ADCs) are agents composed of a monoclonal antibody linked to cytotoxic molecules. By specifically delivering cytotoxic agents to cells expressing surface antigens of interest, ADC technology allows for the targeted use of highly toxic agents resulting in increased efficacy against malignant cells and decreased damage to normal tissue. Effector agents can be small molecules, radioisotopes, proteins, or bacterially derived toxins. Over the past several decades, ADCs have been evaluated in a variety of preclinical models of hematologic malignancies, as well as early-phase clinical trials with limited success. More recently, advancements in linkage technology, improvements in cytotoxin selection, and use of smaller conjugates containing partial rather than complete antibodies have drastically improved the potential clinical value of ADCs. In the future, ADC technology may be used to restore tumor suppressor activity, target the microenvironment, or replace nonfunctional enzymes. In this review we will discuss select ADCs in various stages of development for use in hematologic malignancies including lymphoma, multiple myeloma, and leukemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Video-Audio Media

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / immunology*
  • Biomarkers, Tumor / metabolism
  • Drug Design
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / metabolism
  • Humans
  • Immunoconjugates / adverse effects
  • Immunoconjugates / immunology
  • Immunoconjugates / therapeutic use*
  • Leukemia / drug therapy
  • Leukemia / immunology
  • Leukemia / metabolism
  • Lymphoma / drug therapy
  • Lymphoma / immunology
  • Lymphoma / metabolism
  • Molecular Targeted Therapy*
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / immunology
  • Multiple Myeloma / metabolism
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Immunoconjugates