What makes a good antibody–drug conjugate?

Cecco, Martin De; Galbraith, Daniel; McDermott, Lisa L

doi:10.1080/14712598.2021.1880562

Cited by 38 publications

(27 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AntibodyÀ drug conjugates (ADCs) are well-established cancer therapeutics consisting of a highly active small molecule drug (payload) covalently bonded to an antibody via a linker (Figure 1). [1][2][3][4][5] Currently, > 10 ADCs are commercially available (Table 1) and > 110 ADCs are under investigation in clinical trials. [1] ADCs comprise four segments: the monoclonal antibody, payload, linker, and conjugation site.…”

Section: Overview Of Antibodyà Drug Conjugatesmentioning

confidence: 99%

Tag‐Free Enzymatic Modification for Antibody−Drug Conjugate Production

Yamazaki

Matsuda

2022

ChemistrySelect

View full text Add to dashboard Cite

Currently, although >10 antibody−drug conjugates (ADCs) are available in the market, most of them (10 ADCs) have broad drug distribution, thereby potentially limiting their therapeutic index. The ADC industry is shifting from random conjugation technology to site‐specific conjugation technology to overcome this issue. Enzymatic site‐specific conjugation is a promising cutting‐edge technology owing to its mild conjugation conditions. This review discussed enzymatic conjugation strategies for producing ADCs via modifying native antibodies without using a tag moiety. We described the comparison of the three main conjugation technologies used to produce site‐specific ADCs. Each of the three enzymatic approaches described in this review differs in their advantages and disadvantages, providing pharmaceutical companies the option to select an approach suitable to their purpose and/or target protein.

show abstract

Section: Overview Of Antibodyà Drug Conjugatesmentioning

confidence: 99%

Tag‐Free Enzymatic Modification for Antibody−Drug Conjugate Production

Yamazaki

Matsuda

2022

ChemistrySelect

View full text Add to dashboard Cite

show abstract

“…Trastuzumab-emtansine (T-DM1, commercial name: Kadcyla) is a maytansinoid-based antibody-drug conjugate (ADC), which was first approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer [1]. Since its success in 2013, more than 10 ADCs been introduced into the market [2,3].…”

Section: Introductionmentioning

confidence: 99%

Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®

Seki¹,

Yamada²,

Ooba³

et al. 2022

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

Background: Trastuzumab-emtansine (T-DM1, commercial name: Kadcyla) is well-known antibody-drug conjugate (ADC) and was first approved for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This molecular format consisting of trastuzumab and maytansinoid payload (emtansine) is very simple, however, T-DM1 has wide heterogeneity due to non-specific conjugation, lowering its therapeutic index (TI). Methods: To overcome this issue during the chemical modification of the random conjugation approach to generate T-DM1, we developed a novel chemical conjugation technology termed "AJICAP®" for modification of antibodies in site-specific manner by IgG Fc-affinity peptide based reagents. Results: In this study, we compared site-specific maytansinoidbased ADCs synthesized by AJICAP and T-DM1 in rat safety studies. The results indicated an increase in the maximum tolerated dose, demonstrating an expansion of the AJICAP-ADC therapeutic index compared with that of commercially available T-DM1. Gram scale preparation of this AJICAP-ADC and the initial stability study are also described. Conclusions: Trastuzumab-AJICAP-maytansinoid produced by this unique chemical conjugation methodology showed higher stability and tolerability than commercially available T-DM1.

show abstract

“…Currently, immunotherapeutics, especially antibody-based molecules, hold much promise for treating diseases. Compared to conventional chemotherapeutics or therapeutics of other modalities, antibodies typically show a reduced toxicity profile [ 1 , 2 ]. These biologics have come a long way from their first FDA approval in 1986 to the 100th monoclonal antibody (mAb) approved for therapy in 2021 [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of mammalian proteins for diagnostics and therapeutics: a review

et al. 2022

View full text Add to dashboard Cite

Background Antibodies have proven to be remarkably successful for biomedical applications. They play important roles in epidemiology and medicine from diagnostics of diseases to therapeutics, treating diseases from incessant chronic diseases such as rheumatology to pandemic outbreaks. With no end in sight for the demand for antibody products, optimizations and new techniques must be expanded to accommodate this. Methods and Results This review discusses optimizations and techniques for antibody production through choice of discovery platforms, expression systems, cell culture mediums, and other strategies to increase expression yield. Each system has its own merits and demerits, and the strategy chosen is critical in addressing various biological aspects. Conclusions There is still insufficient evidence to validate the efficacy of some of these techniques, and further research is needed to consolidate these industrial production systems. There is no doubt that more strategies, systems, and pipelines will contribute to enhance biopharmaceutical production.

show abstract

What makes a good antibody–drug conjugate?

Cited by 38 publications

References 56 publications

Tag‐Free Enzymatic Modification for Antibody−Drug Conjugate Production

Tag‐Free Enzymatic Modification for Antibody−Drug Conjugate Production

Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®

Expression of mammalian proteins for diagnostics and therapeutics: a review

Contact Info

Product

Resources

About