Selection of reaction additives used in the preparation of monomeric antibody-calicheamicin conjugates.
The formation of protein aggregates can be a major problem during the preparation of antibody-drug conjugates. Herein is described the methods by which reaction additives were selected, which reduce the tendency of antibodies to aggregate during the attachment of the cytotoxic agent calicheamicin to form an immunoconjugate. Reaction conditions were delineated that produced optimized yields of monomeric conjugates. These conditions were used in the preclinical preparations of gemtuzumab ozogamicin (Mylotarg), the first commercially available chemotherapeutic immunoconjugate.
Hollander
Irwin
I
Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA.
Kunz
Arthur
A
Hamann
Philip R
PR
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000079982:Gemtuzumab; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D000922:Immunotoxins / Q000737:chemistry* / Q000276:immunology; D009930:Organic Chemicals / Q000737:chemistry; D063268:Sialic Acid Binding Ig-like Lectin 3; D014481:United States; D014486:United States Food and Drug Administration
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D007074:Immunoglobulin G; D000922:Immunotoxins; D009930:Organic Chemicals; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab