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Your Position: Home > Antibody-Drug Conjugates (ADCs): the Magic Bullets for Treatment

Antibody-Drug Conjugates (ADCs): the Magic Bullets for Treatment

Antibody-Drug Conjugates (ADCs): the Magic Bullets for Treatment
Background

In recent years, Antibody-Drug Conjugates (ADCs) may serve as a novel therapeutic modality for many cancer patients. Indeed, three key elements define an ADC: the antibody directed against a specific tumor antigen, the cytotoxin/payload and the cleavable/uncleavable linker connecting the payload to the antibody [1]. Specific target recognition and effective toxin make ADCs veritable "magic bullet". These 'magic bullets' deliver treatment that is both highly targeted and highly potent, seeking out and attacking cancerous cells throughout the body, while avoiding harm to healthy cells. Reasonable selection of targets, antibody, linker, payload, and their rational combinations, as well as conjugation methods are crucial for an effective treatment. Among these elements, target selection, linker selection, conjugation methods and evaluating preclinical /clinical efficacy are considered critical factors for ADCs development. >>> Download the ebook: Key point of ADCs design

To meet the needs of ADCs development, ACROBiosystems can provide:
A variety of high-quality target proteins;
MMPs/Cathepsin/uPA for cleavable linker;
ADC site-specific conjugation kits;
Anti-payload antibodies, anti-idiotypic antibodies(ADA) for immunogenicity and PK analysis.
PR/BLI analytical & anti-Idiotypic antibody development service.
Structure of ADCs
All products and services can meet the entire process of ADCs from antibody preparation, initial screening, production to quality control, facilitating your ADCs development.
Hot Products
High-quality ADC target proteins
ADC-related target proteins

Features

  1. >> 50+ ADC targets, such as Trop-2, Nectin-4,LIV-1 and ROR1;

  2. >> Various species & tag;

  3. >> High purity verified by MALS;

  4. >> High bioactivity verified by ELISA / SPR / BLI / FACS, etc.

Applications

  • Suitable for immunization / antibody screening / cross-reactivity/cell-based assay/QC.

Featured products

  • Exclusive LIV-1 proteins:

  • ✔ Multiple species: Human, Mouse, Cynomolgus, Rat, etc.;

  • ✔ Expression sequences were designed based on the SGN-LIV1A binding epitope.

Proteases for peptide linker
Cathepsin B, Proteases for peptide linker in ADCs

Features

  1. >> Comprehensive products: Cathepsin, MMPs and uPA etc.;

  2. >> Natural conformation: HEK293 expressed protein to ensure the natural structure;

  3. >> High enzyme activity: enzyme activity > 2,500 pmol/min/µg.

Applications

  • ✔ Evaluate the effect of proteases cleavage of linker to ensure the efficient release of the intracellular payloads.

Tools for ADCs PK analysis
Anti-MMAE antibodies and anti-idiotypic antibodies for ADCs PK analysis

Features

  1. >> Comprehensive products: anti-MMAE antibodies and anti-idiotypic antibodies;

  2. >> High specificity & affinity;

  3. >> High sensitivity & stability.

Applications

  • ✔ Positive reference of ADCs preclinical / clinical immunogenicity;

  • ✔ PK analysis;

  • ✔ Anti-payload antibodies: Qualitative detection of DAR value.

Featured products

  • The activity of anti-MMAE monoclonal antibody (Cat.No.MME-M5252) is verified by binding to Disitamab Vedotin (RC-48) with a linear range of 0.1-2 ng/mL.

SPR/BLI analytical & ADA development service
SPR /BLI analytical service

SPR /BLI analytical service

  1. ACRO proteins supplied for free

  2. Only your samples are required

  3. Reports follows all IND requirements

    Applications

  • Based on the Biacore 8K and ForteBio Octet platforms, ACROBiosystems provides biopharmaceutical R&D customers with complementary molecular interaction analysis services, including antibody screening, characterization, consistency evaluation, and biomolecule interactions that contribute to therapeutics development.

Anti-Idiotypic Antibody Development Service

Anti-Idiotypic Antibody Development Service

  1. Fast response, one-on-one service

  2. Ensure delivery of PK/ADA test kits with sensitivity

  3. ACRO proteins supplied for free

    Service

  • ✔ Monoclonal/polyclonal anti-idiotype antibody, pharmacokinetic and immunogenicity test kit.

  • Applications

  • ✔ ADA assay: Perfect as Calibrator;

  • ✔ PK assay: Quantitative analysis of therapeutic antibody in matrix.

Product list
  • ADC target proteins

  • Proteases for peptide linker

  • AGLink™ ADC site-specific conjugation kits

  • Tools for ADCs PK analysis

TypeMoleculeCat. No.Product DescriptionPreorder/Order
CathepsinCathepsin BCTB-H5222Human Cathepsin B / CTSB Protein, His Tag (active enzyme)

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PLAUPLAUPLU-H5229Human PLAU / uPA Protein, His Tag

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PLAUPLU-H5228Human PLAU / uPA Protein, His Tag (activated by trypsin) (active enzyme)

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MMPsMMP-1MM1-H5222Human MMP-1 Protein, His Tag

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MMP-2MM2-H82E3Biotinylated Human MMP-2 Protein, His,Avitag™

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MMP-9MM9-H5221Human MMP-9 Protein, His Tag (active enzyme)

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Cat. No.Product DescriptionComponentsPreorder/Order
ADC-P001AGlink ADC Conjugation Kit (MMAE, DAR4)● Enzymatic reagents for conjugation
● Cofactors and substrates for conjugation
● Hydrophilic and potent linker-MMAE
● Optimized purification protocol

Preorder

ADC-P002AGlink ADC Conjugation Kit (MMAE, DAR2)● Enzymatic reagents for conjugation
● Cofactors and substrates for conjugation
● Hydrophilic and potent linker-MMAE
● Optimized purification protocol

Preorder

Cat.No.Product descriptionNeutralizing activityAffinity KD, nMApplication
DXD-AY72NEWMonoclonal Anti-DXD Antibody (5C8A1)//PK assay; ELISA
MME-M5252NEWMouse Anti-MMAE Antibody, Mouse IgG1 (MALS verified)//PK assay; ELISA
ADB-Y19Anti-Adalim*mab AntibodiesNeutralizing Antibody0.0013ADA assay; Neutralizing assay; Indirect ELISA
ADB-Y23bAnti-Adalim*mab AntibodiesNon-Neutralizing Antibody/PK bridging ELISA with ADB-BY17; Indirect ELISA
ADB-BY17Biotinylated Anti-Adalim*mab AntibodiesNeutralizing Antibody/PK bridging ELISA with ADB-Y23b
BEB-Y9Anti-Bevaciz*mab AntibodiesNeutralizing Antibody1.92ADA assay; Indirect ELISA
BEB-Y10Anti-Bevaciz*mab AntibodiesNeutralizing Antibody/PK bridging ELISA with BEB-BY13; Neutralizing assay; Indirect ELISA
BEB-BY13Biotinylated Anti-Bevaciz*mab AntibodiesNeutralizing Antibody/PK bridging ELISA with BEB-Y10
CEB-Y27Anti-Cetux*mab AntibodiesNeutralizing Antibody0.007ADA assay; Neutralizing assay; Indirect ELISA
CEB-Y29Anti-Cetux*mab AntibodiesNeutralizing Antibody/PK bridging ELISA with CEB-BY31; Neutralizing assay; Indirect ELISA
CEB-BY31Biotinylated Anti-Cetux*mab AntibodiesNon-Neutralizing Antibody/PK bridging ELISA with CEB-Y29
RIB-Y35cAnti-Ritux*mab AntibodiesNeutralizing Antibody/ADA assay; Neutralizing assay; Indirect ELISA
TRB-Y1bAnti-Trastuz*mab AntibodiesNeutralizing Antibody/PK bridging ELISA with TRB-Y5b; Neutralizing assay; Indirect ELISA
TRB-Y5bAnti-Trastuz*mab AntibodiesNon-Neutralizing Antibody/PK bridging ELISA with TRB-Y1b
High-quality ADC target proteins
TROP-2
                   
Nectin-4
                   
EGFR
                   
Her2
                   
CEACAM-5
                   
CD79B
                   
PSMA
                   
Claudin18.2
                   
FOLR1
                   
Siglec-3
                   
BCMA
                   
Siglec-2
                   
CD19
                   
CD30
                   
DLL3
                   
PTK7
                   
TF
                   
TF
                   
ROR1
                   
ENPP3
                   
LIV-1
                   
HGFR
                   
NCAM-1
                   
EGFRvIII
                   
CD133
                   
LY75

Case study

High purity verified by MALS
HER2, MALS-validated protein

The purity of Human Her2, His Tag (Cat. No. HE2-H5225) was more than 90% and the molecular weight of this protein is around 80-95 kDa verified by SEC-MALS.

High affinity validated by ELISA
HER2 protein's affinity verified by ELISA

Immobilized Human TROP-2, His Tag (Cat. No. HE2-H5225) at 1 μg/mL (100 μL/well) can bind Mouse Monoclonal Antibody Against Human TROP-2, Mouse IgG1 with a linear range of 0.1-2 ng/mL (QC tested).

PSMA protein's affinity verified by ELISA

Immobilized Human PSMA, His Tag (Cat. No. PSA-H52H3) at 2 μg/mL (100 μL/well) can bind Monoclonal Anti-Human PSMA Antibody, Human IgG1 with a linear range of 0.3-39 ng/mL (Routinely tested).

High affinity validated by SPR
LIV-1 protein's affinity verified by SPR

Anti-LIV-1 mAb captured on CM5 chip via anti-human IgG Fc antibody can bind Human LIV-1, His Tag (Cat. No. LV1-H5223) with an affinity constant of 5.24 nM as determined in a SPR assay (Biacore T200) (Routinely tested).

HER2 protein's affinity verified by SPR

Trastuz*mab captured on CM5 chip via anti-human IgG Fc antibodies surface, can bind Human Her2, His Tag (Cat. No. HE2-H5225) with an affinity constant of 1.07 nM as determined in a SPR assay.

High affinity validated by BLI
Nectin-4 protein's affinity verified by BLI

Loaded Mouse Nectin-4, His Tag (Cat. No. NE4-M52H3) on HIS1K Biosensor, can bind Human Nectin-1, Fc Tag (Cat. No. PV1-H5253) with an affinity constant of 0.12 μM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).

High affinity validated by FACS
ROR1 protein's affinity verified by BLI

2e5 of anti-ROR1 CAR-293 cells were stained with 100 μL of 10 μg/mL of Human / Cynomolgus / Rhesus macaque ROR1 (39-151, Ig-like domain), His Tag (Cat. No. RO1-H5221) and negative control protein respectively, washed and then followed by PE-anti-His Tag and analyzed with FACS (Routinely tested).

Proteases for peptide linker
In the design and development of ADC, linker affects the stability of ADCs in systematic circulation, the speed of lysosomal processing, etc. There are two main categories of ADC linkers in current ADC drugs, cleavable linkers, and non-cleavable linkers.
Peptide linker as a protease-sensitive cleavable linker, is used in most ADCs that are undergoing clinical testing.  In the design of peptide linker, it is necessary to consider the selection of a suitable protease for linker cleavage, such as: MMPs/Cathepsin/ PLAU [2].
Thus, ACROBiosystems has developed a series of MMPs, Cathepsin and uPA protein products for cleavage of Linker.
More anti-payload antibodies (Anti-Dxd antibody/Anti-SN-38 antibody/Anti-SN-38 antibody) are coming soon!
Mechanisms of action of ADCs

Case study

ProductsCat.No:CTB-H5222 Human Cathepsin B / CTSB Protein, His Tag (active enzyme)Cat.No:MM9-H5221 Human MMP-9 Protein, His Tag (active enzyme)
Hydrolyzed substrateFluorogenic peptide substrate Z-LR-AMCFluorogenic peptide substrate Mca-PLGL-Dpa-AR-NH2
Enzymatic activity
(pmol/min/μg)
> 2500> 2500
ADC site-specific conjugation kits
Conjugation methods are generally divided into random conjugation and site-specific conjugation. Random conjugation can cause several problems, including suboptimal therapeutic index, narrower therapeutic windows, and poor stability. Site-specific conjugations are designed to overcome the heterogeneity observed with ADCs that use random conjugation to surface-exposed lysine residues or conjugation to interchain disulfide bonds. Site-specific conjugation can precisely control conjugation sites, producing a homogenous mixture that yields higher potency ADC’s.
The characteristics of various conjugation methods applied for ADCs
The characteristics of various conjugation methods applied for ADCs[3]
AGLink ADC site-specific conjugation kits are co-developed by ACROBiosystems and Glyco-therapy Biotechnology Co., Ltd. based on the conjugation platform (YTConjuTM) owned by Glyco-therapy Biotechnology Co., Ltd.[4]. AGLink enables enzymatic modification of IgG Fc glycans that result in homogenous conjugates, which can be used for early scientific research of ADCs.

Mechanism of conjugation

All monoclonal antibodies are glycosylated at (or around) asparagine 297 (N297). The inherent site specificity of Fc glycosylation makes the glycoengineering being recognized as a universal and efficient approach to synthesize homogeneous antibody conjugates. Schematic diagrams are as follows [4]
AGlink ADC Conjugation Kit (MMAE, DAR4)
AGlink ADC Conjugation Kit (MMAE, DAR4)
AGlink ADC Conjugation Kit (MMAE, DAR2)
AGlink ADC Conjugation Kit (MMAE, DAR2)

Assay Data

High homogeneity conjugated antibodies
HIC-HPLC analysis of MMAE ADCs (DAR 4 & DAR 2)

HIC-HPLC analysis of MMAE ADCs (DAR 4 & DAR 2)

Preserved immunoreactivity after conjugation
The analysis of the antigen-binding capacity of MMAE ADCs (DAR 4 & DAR 2)

The analysis of the antigen-binding capacity of MMAE ADCs (DAR 4 & DAR 2), the results showing that binding to the HER2 antigen unaffected by the AGLink conjugation

Consistency in the site-specific labeling process ensures mitigate the aggregation
Less than 5% of antibody aggregation by SEC-HPLC

Less than 5% of antibody aggregation by SEC-HPLC

The conjugates have high in-vitro plasma stability
The conjugates have high in-vitro plasma stability

MMAE ADCs (DAR 4 & DAR 2) are stable in human plasma in vitro

In-vitro cell-killing activity assay
In-vitro cell-killing activity assay

Validated in-vitro cell-killing activity of MMAE ADCs (DAR 4 & DAR 2)

PK analysis
Supporting Immunogenicity and PK analysis, ACRO provides series of anti-MMAE antibodies, anti-DXD antibody and anti-idiotypic antibodies with high affinity, high specificity and high sensitivity.
Used for the positive reference of ADCs preclinical/clinical immunogenicity and PK analysis;
Save customer's time to prepare antibodies;
Complete methodology protocols are available freely.

Case study

PK assay: Anti-MMAE antibody binding MMAE with high specificity
Anti-MMAE antibody binding MMAE with high specificity

The EC50 value of anti-MMAE antibody to MMAE-conjugated hRS7 (MMAE-ADC) was 0.12 μg/ml. The unconjugated hRS7 antibody was used as negative control

Anti-MMAE antibody binding MMAE-ADC with high specificity

Immobilized Disitamab Vedotin (RC48) at 0.2 μg/mL (100 μL/well) can bind Mouse Anti-MMAE Antibody, Mouse IgG1 (Cat. No. MME-M5252) with a linear range of 0.1-2 ng/mL (QC tested).

PK assay: Specific detection of antibody drug levels in the body
PK assay for ADCs: Specific detection of antibody drug levels in the body
Detection of Ritux*mab by antigen-capture ELISA (0.1% serum).
PK assay for ADCs: Specific detection of antibody drug levels in the body
Detection of Ritux*mab by anti-idiotypic capture ELISA (0.1% serum).
PK assay for ADCs: Specific detection of antibody drug levels in the body
Detection of Ritux*mab by anti-idiotypic bridging ELISA (10% serum).
MethodCoatedSampleLinear range
(µg/mL)
Sensitivity
(µg/mL)
Advantage
Antigen capture ELISACD20Goat anti-human IgGSimple and universal method
Anti-idiotypic capture ELISAAnti-Ritux*mab AntibodiesGoat anti-human IgG0.156-100.156It is a simple method for extracting CD20
Bridging ELISA by anti-idiotypic antibodiesAnti-Ritux*mab AntibodiesBiotinylated Anti-Ritux*mab Antibodies0.012-0.780.012CD20 can be obtained with good sensitivity and low background noise
Comparison between anti-idiotypic capture ELISA and anti-idiotypic bridging elisa for Ritux*mab detection in patient samples
SPR/BLI analytical service & Anti-idiotypic antibody development service
In addition, relying on a very capable and highly professional team, ACROBiosystems also provides customers with high-quality integrated SPR&BLI analytical service and one-stop services about monoclonal/polyclonal anti-idiotype antibody, facilitating your ADCs development.
SPR/BLI analytical service
Cooperated with hundreds of industrial and scientific research users;
Proteins offered for free;
High standard quality management control system;
Next day reports at the earliest;
Support more than 300 drugs until clinical applications.
SPR/BLI analytical in ADCs
Anti-idiotypic antibody development service
ACRO proteins supplied for free;
Quick response, one-to-one service from the project team, real-time follow-up;
Provide one-stop service from antigen preparation to detection kit development;
Guaranteed delivery of PK/ADA detection reagents whose sensitivity meets regulatory requirements.
Anti-idiotypic antibody development service in ADCs

References

[1]Criscitiello C, et al. Antibody-drug conjugates in solid tumors: a look into novel targets. J Hematol Oncol. 2021 Jan 28;14(1):20.

[2]Poreba M. Protease-activated prodrugs: strategies, challenges, and future directions. FEBS J. 2020 May;287(10):1936-1969.

[3] Antibody drug conjugate: the “biological missile” for targeted cancer therapy

[4] Reducing the Complexity of Fc Glycan Enables the Construction of Antibody Conjugates with Unexpected High Efficiency and Payload Capacity via Glycoengineering

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