Antibody-drug conjugate technology development for hematologic disorders.
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.
Weill Medical College/Cornell University, New York-Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Neil H
NH
Bander
Myron S
MS
Czuczman
Anas
A
Younes
D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000079963:Brentuximab Vedotin; D002986:Clinical Trials as Topic; D000079982:Gemtuzumab; D006689:Hodgkin Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D000080045:Inotuzumab Ozogamicin; D017728:Lymphoma, Large-Cell, Anaplastic / Q000276:immunology / Q000628:therapy*; D008453:Maytansine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D012008:Recurrence
D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D009025:Morpholines; D008453:Maytansine; D000079963:Brentuximab Vedotin; D000079982:Gemtuzumab; C569646:coltuximab ravtansine; D000080045:Inotuzumab Ozogamicin