Abstract
Aim:Direct analytical comparison of two major drug-linkers in the antibody-drug conjugate (ADC) field was conducted.Methods:Four different analytical methods [AlogP calculation, reverse phase (RP) high-performance liquid chromatography (HPLC; RP-HPLC), size exclusion chromatography HPLC (SEC-HPLC), and differential scanning calorimetry (DSC)] were tested for this comparison.Results:Maytansinoid-based ADCs showed less hydrophobicity than auristatin-based ADCs. Regardless of the drug-linker and drug-to-antibody ratios (DARs), the stability detected by DSC was decreased by conjugation.Conclusions:The cost and time-efficient analytical comparison described in this manuscript may be useful information for an initial characterization of ADCs prior to detailed biological studies.
Highlights
Antibody-drug conjugates (ADCs) are a promising biopharmaceutical modality in the oncology field due to the selectivity against their target [1,2,3,4]
The present results to compare MMAE and maytansinoid were supported by reverse phase (RP)-high-performance liquid chromatography (HPLC) analysis, this calculation could be considered the use for the structure activity relationship study of MMAE
RP-HPLC analysis of ADC was used in the present study for assessment of hydrophobicity of ADCs as well as drug-to-antibody ratios (DARs) determination
Summary
Antibody-drug conjugates (ADCs) are a promising biopharmaceutical modality in the oncology field due to the selectivity against their target [1,2,3,4]. These bioconjugates are produced via linking small molecules (drug-linkers) to monoclonal antibodies possessing a binding affinity for a tumor-associated target antigen in a specific manner. The key factor for ADC efficacy is the choice of the drug-linker compounds These small cytotoxic molecules are familiar to traditional synthetic organic chemists [5]. A wide variety of natural products have been reported, some of which have the potential to be used as payloads This tremendous natural products toolbox has not been utilized effectively in the field of ADCs and currently, only a handful of natural compound analogs have been applied successfully to ADCs [6]. The synthesis of these ADCs can result in a very large number of species because the antibodies have about 80 exposed and reactive lysine residues available for conjugation (Figure 1A, 1B)
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