IMR Press / FBL / Volume 27 / Issue 8 / DOI: 10.31083/j.fbl2708234
Open Access Original Research
Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®
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1 Ajinomoto Co., Inc., 1-1, Suzuki-Cho, Kawasaki-Ku, Kawasaki-Shi, 210-8681 Kanagawa, Japan
2 Ajinomoto Bio-Pharma Services, San Diego, CA 92121, USA
*Correspondence: (Yutaka Matsuda); (Tatsuya Okuzumi)
§Present addresses: Exelixis Inc., Alameda, CA 94502, USA
Academic Editor: Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(8), 234;
Submitted: 31 May 2022 | Revised: 4 July 2022 | Accepted: 21 July 2022 | Published: 5 August 2022
(This article belongs to the Special Issue Antibody Drug Conjugates)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

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 maytansinoid-based 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.

antibody drug conjugate
toxicology study
site-specific conjugation
Fig. 1.
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