Abstract
Advances in antibody–drug conjugates (ADCs) will permit sensitive discrimination between healthy and cancer cells. Promising clinical results generated much hope that this targeted prodrug therapy will offer more effective treatment options to patients. Manufacturing such highly potent biopharmaceuticals presents a series of unique challenges. Some specific skills required for the process development and production of ADCs are discussed. In addition to the accuracy and reliability needed to handle these potent and costly materials, coworker safety and equipment cleaning are of particular importance. The ideas and concepts shared in this article are based on the experience that Lonza has gained in the ADC field since 2004.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Wu AM, Senter PD (2005) Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 23:1137–1146
Ricart AD, Tolcher AW (2007) Technology insight: cytotoxic drug immunoconjugates for cancer therapy. Nat Clin Pract Oncol 4:245–255
Carter PJ, Senter PD (2008) Antibody-drug conjugates for cancer therapy. Cancer J 14:154–169
Kratz F, Müller IA, Ryppa C, Warnecke A (2008) Prodrug strategies in anticancer chemotherapy. ChemMedChem 3:20–53
Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:235–244
Alley SC, Okeley NM, Senter PD (2010) Antibody-drug conjugates: targeted drug delivery for cancer. Curr Opin Chem Biol 14:529–537
Mathé G, Loc TB, Bernhard J (1958) Effet sur la leucémie 1210 de la souris d’une combinaison par diazotation d’A-méthopérine et de γ-globulines de hamsters porteurs de cette leucémie par hétérogreffe. C R Hebd Seances Acad Sci 246(10):1626–1628
Ducry L, Stump B (2010) Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 21:5–13
Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Blättler WA, Lambert JM, Chari RVJ, Lutz RJ, Wong WLT, Jacobson FS, Koeppen H, Schwall RH, Kenkare-Mitra SR, Spencer SD, Sliwkowski MX (2008) Targeting HER2-positive breast cancer with Trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 68:9280–9290
Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, Girish S, Tibbitts J, Yi J-H, Sliwkowski MX, Jacobson F, Lutzker SG, Burris HA (2010) Phase I study of Trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol 28:2698–2704
Bartlett N, Forero-Torres A, Rosenblatt J, Fanale M, Horning SJ, Thompson S, Sievers EL, Kennedy DA (2009) Complete remissions with weekly dosing of SGN-35, a novel antibody-dug conjugate (ADC) targeting CD30, in phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). J Clin Oncol 27:8500, Abstract
Okeley NM, Miyamoto JB, Zhang X, Sanderson RJ, Benjamin DR, Sievers EL, Senter PD, Alley SC (2010) Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res 16:888–897
DiJoseph JF, Dougher MM, Kalyandrug LB, Armellino DC, Boghaert ER, Hamann PR, Moran JK, Damle NK (2006) Antitumor efficacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin’s B-cell lymphoma. Clin Cancer Res 12:242–249
DiJoseph JF, Khandke K, Dougher MM, Evans DY, Armellino DC, Hamann PR, Damle NK (2008) CMC-544 (inotuzumab ozogamicin): a CD22-targeted immunoconjugate of calicheamicin. Hematology Meeting Reports 5:74–77
Wakankar AA, Feeney MB, Rivera J, Chen Y, Kim M, Sharma VK, Wang YJ (2010) Physicochemical stability of the antibody-drug conjugate Trastuzumab-DM1: changes due to modification and conjugation processes. Bioconjug Chem 21:1588–1595
Magalhães PO, Lopes AM, Mazzola PG, Rangel-Yagui C, Penna TCV, Pessoa A Jr (2007) Methods of endotoxin removal from biological preparations: a review. J Pharm Sci 10:388–404
Wakankar A, Chen Y, Gokarn Y, Jacobson FS (2011) Analytical methods for physicochemical characterization of antibody drug conjugates. mAbs 3:164–175
Stephan JP, Kozak KR, Wong WLT (2011) Challenges in developing bioanalytical assays for characterization of antibody–drug conjugates. Bioanalysis 3:677–700
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Ducry, L. (2012). Challenges in the Development and Manufacturing of Antibody–Drug Conjugates. In: Voynov, V., Caravella, J. (eds) Therapeutic Proteins. Methods in Molecular Biology, vol 899. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-921-1_29
Download citation
DOI: https://doi.org/10.1007/978-1-61779-921-1_29
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-920-4
Online ISBN: 978-1-61779-921-1
eBook Packages: Springer Protocols