Antibody-drug conjugate technology development for hematologic disorders Journal Article


Authors: Bander, N. H.; Czuczman, M. S.; Younes, A.
Article Title: Antibody-drug conjugate technology development for hematologic disorders
Abstract: Antibody-drug conjugates (ADCs) combine cytotoxic chemotherapy and antibody specificity. There are 4 components of ADC technology: the cancer, or target, antigen; the antibody to that target; the linker that connects the drug to the antibody; and the drug itself. The antibody directs the cytotoxic agent to the tumor cell, thereby diminishing the side effect profile of the cytotoxic agent and enabling delivery of a more potent therapeutic because of the ability to control the target and the side effects. ADC technology has vastly improved within the last several years. In early ADCs, the linkers were too labile, which led to the release of free drug in the circulation and consequent off-target toxicity. In the current generation of ADCs, the linkers are more stable, and the cytotoxic agents are significantly more potent. ADCs have been developed against a variety of antigens and receptors, including CD19, CD22, and CD30, and have been linked to multiple different cytotoxic agents, including calicheamicin and maytansinoid derivatives. The ADC brentuximab vedotin was recently approved by the US Food and Drug Administration for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or at least 2 prior multiagent chemotherapy regimens, and the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least 1 prior multiagent chemotherapy regimen. Other ADCs in clinical trials for hematologic disorders include inotuzumab ozogamicin, SAR3419, and gemtuzumab ozogamicin.
Keywords: antineoplastic agents; clinical trials as topic; methodology; antineoplastic agent; recurrence; hodgkin disease; monoclonal antibody; immunology; immunotherapy; morpholines; drug derivative; recurrent disease; large cell lymphoma; antigens, cd; leukocyte antigen; maytansine; clinical trial (topic); aminoglycoside; aminoglycosides; inotuzumab ozogamicin; lymphoma, large-cell, anaplastic; antibody conjugate; immunoconjugates; gemtuzumab; antibodies, monoclonal, humanized; morpholine derivative; cac10 vcmmae; cac10-vcmmae; sar 3419
Journal Title: Clinical Advances in Hematology & Oncology
Volume: 10
Issue: 8 Suppl 10
ISSN: 1543-0790
Publisher: Millennium Medical Publishing, Inc  
Date Published: 2012-08-01
Start Page: 1
End Page: 16
Language: English
PUBMED: 23072775
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 4 September 2013" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Neil Harrison Bander
    62 Bander