Effects of Drug Loading on the Antitumor Activity of a Monoclonal Antibody Drug Conjugate

By Kevin J. Hamblett, P. Senter, D. Chace, Michael M C Sun, J. Lenox, C. Cerveny, K. Kissler, Starr X Bernhardt, Anastasia K Kopcha, R. Zabinski and 2 more. Clinical Cancer Research, 2004

1,067 citations recorded by the source corpus.

Subfields: Immunology and Allergy, Oncology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/226a613ca9c8cc671afd7d1e3e3943c15ee46ac0

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Citations in the corpus

Antibody targeted drugs as cancer therapeutics (2006, background): “For instance, increasing the number of monomethyl auristatin E molecules fused per antibody above an optimal number demonstrated only equivalent antitumour activity accompanied by increased toxicit”
Antibody Structure and Function: The Basis for Engineering Therapeutics (2019, background): “An increase in pharmacokinetic stability likely contributed to this effect, as the ADCs with reducible linkers were more likely to lose the payload before delivery to target cells.”
Antibody Drug Conjugates for Cancer Therapy (2016, background): “Despite derivatization of all eight interchain cysteine residues with MMAE, these purified ADCs appear identical in size to underivatized native IgG, bind target, and kill cells in vitro with potency commensurate with their high drug load (Hamblett et al., 2004; Adem et al., 2014).”
DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1 (2016, background): “ADCs with greater DAR (DAR 6 and 8) are generally unstable and show higher clearances, which can result in decreasing efficacy and increasing toxicity (24).”
Site-specific antibody drug conjugates for cancer therapy (2013, background): “As described above, this process involves partial reduction of inter-chain disulfide bonds and results in a heterogeneous mixture of ADCs that differ with respect to site of conjugation, number of drugs per antibody, and number of intact inter-chain disulfide bonds.(42) To avoid the problem of heter”
Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates (2012, methodology): “Thiol-maleimide chemistry is a commonly used method, whereby a cysteine residue, either native or engineered, is used for conjugatio”