Antibody-drug conjugates (ADCs) are composed of monoclonal antibodies targeting tumor-specific or tumor-associated antigens, linked to cytotoxic small-molecule drugs (payloads) via linkers. Combining the high targeting of monoclonal antibodies and the high activity of cytotoxic drugs in tumor tissues, ADCs are one of the fastest-growing categories of drugs in the field of tumor-targeted therapy in recent years.

How is ADC conjugation performed?

The mainstream method currently used is cysteine conjugation. By adding a reducing agent, the interchain disulfide bonds of the antibody are reduced at a specific temperature to generate free thiol groups. Subsequently, payload with a linker is added, and the maleimide on the linker reacts with the thiol group through Michael addition, thereby conjugating the small-molecule drug to the antibody.

How do ADC drugs work?

(1)Antigen Binding: ADCs circulate in the bloodstream, finding and binding to their cellular targets. Non-specific binding can lead to off-target toxicity. (2)Endocytosis: The mAb component of the ADC binds to FcRn, which is mainly expressed in endosomes. The ADC is then recycled back to the cell surface and exposed to physiological pH, releasing it from FcRn and extending its half-life in vivo. (3)Lysosomal Degradation: For ADCs with cleavable linkers, the cleavage mechanism(e.g., hydrolysis, protease-mediated cleavage, or reductive cleavage of disulfide bonds) occurs in early or late endosomes without progressing to lysosomal transport. For ADCs with non-cleavable linkers, the proton pumps on lysosomes create an acid-unstable environment that promotes ADC degradation and protease-mediated hydrolysis (e.g., by cathepsin B and plasmin). (4)Payload Release: The ADC undergoes catabolism and releases the toxic payload, which is then transported from the lysosomal lumen to the cytoplasm. (5)Target Cell Apoptosis: The cytotoxic drug induces cell apoptosis or other forms of cell death by inter.

ADCハイスループット抗体結合

サービス概要

抗体薬物複合体（ADC： Antibody-drug conjugates）は、抗体の治療効果を高めることを目的として設計された、「マジック・ブレット（魔法の弾丸）」とも呼ばれる新しいタイプのバイオ医薬品です。現在、ADCは主にがん領域で広く使用されており、他の疾患を対象としたADCの開発も進められています。

ADCは、ガン細胞の表面抗原を特異的に認識し、結合している高い活性低分子薬物毒素を利用して、標的の腫瘍細胞を殺傷することができます。低分子治療薬に比べて、ADCは抗原陽性の腫瘍細胞に対する高い特異性を示すため、オフターゲット効果による正常組織への毒性を減らし、さらに半減期が長いという利点も備えています。

当社のADCコンジュゲーションプラットフォームは、抗体発現およびエンジニアリングプラットフォームの強みと組み合わせることで、抗体の発現、コンジュゲーション、品質評価に至るまで、一貫したサービスプロセスを提供できます。前臨床段階におけるADCのスクリーニング、試験、評価のニーズに対応することが可能です。

ハイライト

カスタム抗体コンジュゲーションサービス

自社製およびお客様提供の低分子薬物のいずれにもコンジュゲーション可能
DAR（薬物抗体比）のカスタマイズが可能

多様な抗体およびタンパク質種類

従来型モノクローナル抗体
複雑な二重特異性抗体
非標準アミノ酸（ncAA）を用いたコンジュゲーション

高品質なサービス

作業：2〜3週間
納品物のカスタマイズが可能
試験結果付きの分析レポートを提供

作業フローチャート

システインコンジュゲーション

抗体

①TCEP還元

②リンカーペイロードの添加

粗製ADC製品

フィルトレーション

SECまたはHICによる精製

最終ADC産物

品質管理

ADCハイスループット抗体結合サービスの詳細

納品	濃度：≥1 mg/mL 純度：≥95%（SEC-HPLC） DAR：顧客の要求に応じて設定エンドトキシン：≤1 EU/mg 品質検査：HIC／RP-HPLC／LC-MS 遊離薬物残留：≤5%

納品
- 濃度：≥1 mg/mL
- 純度：≥95%（SEC-HPLC）
- DAR：顧客の要求に応じて設定
- エンドトキシン：≤1 EU/mg
- 品質検査：HIC／RP-HPLC／LC-MS
- 遊離薬物残留：≤5%

事例研究

Case 1: HTP Conjugation

ExperimentalPurpose: Antibody IgG-small molecule drug conjugate (cysteine conjugate), high-throughput screening of DAR4\DAR8 antibody-drug conjugates.

Experimental Results: These antibodies were conjugated with the same drug after expression, and they did not aggregate and the DAR values were uniform.

ADC Case Study-DAR4 HTP Conjugation

ADC Case Study-DAR8 HTP Conjugation

Case 2: CrossAb DAR4 Conjugation

Experimental Results: Using mass spectrometry analysis, the obtained DAR4 antibodies were detected. Through abundance value analysis, the approximate location of small molecule random conjugation was determined.

Chain Name	Modification	Intensity	Average DAR
Heavy Chain	0*Drug	x.xxE+06	4.15
	1*Drug	x.xxE+07
	2*Drug	x.xxE+07
	3*Drug	x.xxE+06
Light Chain 1	0*Drug	x.xxE+06
Light Chain 1	1*Drug	x.xxE+06
Light Chain 2	0*Drug	x.xxE+06
Light Chain 2	1*Drug	x.xxE+06

Case 3: ncAA Click Conjugation

Experimental Purpose: To use ncAA conjugate libraries to screen DAR2\DAR4 antibody conjugates.

UAA Type	Antibody	Linker Payload	DAR
pAMF-Single	mAb	DBCO-PEG4-Val-Cit-PAB-MMAF	DAR2
pAMF-Double	mAb	DBCO-PEG4-Val-Cit-PAB-MMAF	DAR4

Experimental Results: By utilizing ncAA pairs, the DAR2 antibody heavy chain successfully introduced a single azide-containing ncAA and successfully linked a small drug molecule to the ncAA. The obtained DAR4 antibody heavy chain successfully introduced two azide-containing ncAA and successfully linked a small drug molecule to the ncAA.

Chain	PTM	Measured MW (Da)	Intensity	Frac(%)	DAR
Heavy Chain	0*Drug	49548.02	0	0	2
Heavy Chain	1*Drug	51219.66	9.03E+07	100
Light Chain	0*Drug	23438.07	5.65E+08	100
Heavy Chain	0*Drug	49577.02	0	0	3.74
	1*Drug	51219.27	1.13E+07	13.06%
	2*Drug	52946.83	7.52E+07	86.96%
Light Chain	0*Drug	23438.23	7.61E+08	100

FAQs

What are ADC drugs?

Antibody-drug conjugates (ADCs) are composed of monoclonal antibodies targeting tumor-specific or tumor-associated antigens, linked to cytotoxic small-molecule drugs (payloads) via linkers. Combining the high targeting of monoclonal antibodies and the high activity of cytotoxic drugs in tumor tissues, ADCs are one of the fastest-growing categories of drugs in the field of tumor-targeted therapy in recent years.
How is ADC conjugation performed?

The mainstream method currently used is cysteine conjugation. By adding a reducing agent, the interchain disulfide bonds of the antibody are reduced at a specific temperature to generate free thiol groups. Subsequently, payload with a linker is added, and the maleimide on the linker reacts with the thiol group through Michael addition, thereby conjugating the small-molecule drug to the antibody.
How do ADC drugs work?
- (1)Antigen Binding: ADCs circulate in the bloodstream, finding and binding to their cellular targets. Non-specific binding can lead to off-target toxicity.
- (2)Endocytosis: The mAb component of the ADC binds to FcRn, which is mainly expressed in endosomes. The ADC is then recycled back to the cell surface and exposed to physiological pH, releasing it from FcRn and extending its half-life in vivo.
- (3)Lysosomal Degradation: For ADCs with cleavable linkers, the cleavage mechanism(e.g., hydrolysis, protease-mediated cleavage, or reductive cleavage of disulfide bonds) occurs in early or late endosomes without progressing to lysosomal transport. For ADCs with non-cleavable linkers, the proton pumps on lysosomes create an acid-unstable environment that promotes ADC degradation and protease-mediated hydrolysis (e.g., by cathepsin B and plasmin).
- (4)Payload Release: The ADC undergoes catabolism and releases the toxic payload, which is then transported from the lysosomal lumen to the cytoplasm.
- (5)Target Cell Apoptosis: The cytotoxic drug induces cell apoptosis or other forms of cell death by inter.