title: Investigational antibody-drug conjugates for hematological malignancies.
abstract: BACKGROUND
  Antibody-drug conjugates (ADCs) consist of potent cytotoxic drugs linked to antibodies via chemical linkers. ADCs facilitate the specific targeting of drugs to neoplastic cells. This technology is showing efficacy with manageable toxicity for the treatment of hematological malignancies.
  
  
  METHODS
  ADCs for the treatment of hematological malignancies are in pre-clinical and early clinical trials. This review describes these ADCs in detail and explores the challenges of optimizing the use of this technology.
  
  
  RESULTS
  The reader should understand that, although ADCs are conceptually simple, the application of this idea to practice has not been straightforward, and the challenges of developing ADCs include identifying targets with appropriate expression profiles and biology, developing successful linker chemistries, and the selection of a potent cytotoxic drug.
  
  
  CONCLUSIONS
  Hematological malignancies are particularly suited to the development of ADC therapeutics as their surface proteins are well characterized, and the consequences of expression of the target in the normal tissue like the bone marrow results in manageable toxicities since, in many cases, the normal tissue can regenerate. While this technology is complex, the ADCs for hematological malignancies currently in clinical use show great promise.
authors.affiliation: Genentech, Inc., Department of Translational Oncology, 1 DNA way, Mail Stop 72A, South San Francisco 94080, CA, USA. Polson@gene.com
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Polson
authors.forename: William Y
authors.initials: WY
authors.lastname: Ho
authors.forename: Vanitha
authors.initials: V
authors.lastname: Ramakrishnan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D015507:Drugs, Investigational