Antibody-drug conjugates (ADCs) enhance anti-tumor efficacy by targeting cytotoxic drugs to tumor cells through monoclonal antibodies, minimizing damage to normal tissues. The document discusses the structure, mechanism of action, and potential toxicity risks of ADCs, emphasizing the importance of components like linkers and the antibody's characteristics. Furthermore, it highlights developmental trends and the need for precise drug-antibody ratios to optimize treatment outcomes.

1. Antibody-drug Conjugates
www.creative-biolabs.com/adc
Antiboby-drug Conjugate

2. Introduction
Antiboby-drug Conjugate
contents
01
Structure of ADC
02
Action Mechanism
03
Toxicity risk of ADC
04
Development trend
05
About us
06

3. 01. Introduction
Advantage
The antibody-drug conjugate (ADC) perfectly binds cytotoxic drugs to
monoclonal antibodies through chemical bonds, and the cytotoxic
drugs can be "accurately" transported to tumor cells by using the
specific recognition of tumor cells by antibodies.
ADC drugs not only increase the drug concentration in the tumor site,
but also reduce the drug concentration in normal tissues and organs,
and achieve the anti-tumor effect of high efficiency and low toxicity.
ADCs perfectly shows the advantages of high activity of cytotoxic drugs
and high selectivity of antibody, and avoids the shortcomings of
cytotoxic drugs with systemic toxicity and poor anti-tumor efficacy of
antibodies.
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4. Its main components include antibody, linker and small molecule cytotoxic drug (SM). Among them, antibody molecules mainly play the role of targeted drugs
delivery, while small molecular drugs are responsible for the anti-tumor effect.
02.Structure of ADC
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5. Binding
sites:
Binding sites: lysine or
cysteine residues are
generally present at the
junction sites, which can be
modified for directional
coupling.
Linker:
the linker needs to be
stable in circulation and
can be released in the cell
(such as release by
restriction endonuclease in
lysosome, or release after
antibody degradation).
Cytotoxic
drugs:
the conjugated drugs
need to have a high
degree of
pharmacodynamics, no
immunogenicity, and
can bind to the linker
through modification,
and the mechanism is
clear.
02.Structure of ADC
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Selection
of
antibody:
the target of antibody was
clear, high expression in
tumor cells and low
expression in normal tissue;
the antibody could
supported drug loading,
and has good
pharmacokinetic
characteristics and less
non-specific binding. In
addition, In addition,
antibodies are stable and
can internalize into cells.

6. 03.Action Mechanism
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Interalization
Degradation
Break
Release
Binding
1
2
3
4
5

7. Antibody molecule4.1
First of all, antibody molecules, as biological macromolecules, have the toxicity risk of
general biological macromolecules, such as immunogenicity and immunotoxicity, as well
as the possible ADCC effect of monoclonal antibody, CDC action, renal basement
membrane immune complex deposition and so on.
Secondly, if the antibody selectivity is poor or the antigen exists in normal tissue, it will
cause cytotoxic drugs to be delivered to normal cells, resulting in targeted toxicity.
Thirdly, if the Fc fragment of the antibody molecule still has the activity of binding to
immune cell Fc receptors such as Fc γ Rs/FcRN, it is easy to bind to immune cells,
resulting in the killing of immune cells.
Finally, ADC drugs, as exogenous biomolecules, may also phagocytize cells in circulation
and enter the cells through cytosolic action, resulting in cell death.
04.Toxicity risk of ADC
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8. Linker
The stability of the linker directly affects the non-expected dissociation of cytotoxic
drugs. This fragmentation results in the exposure of small molecular cytotoxic drugs in
vivo, that is, off-target toxicity.
Hydrazone bond can be hydrolyzed under acidic conditions and is a relatively unstable
connector.
Disulfide bonds can be hydrolyzed in a high concentration of glutathione in the cell, so
it is not easy to fall off outside the cell.
The binding of peptide bond is the most close, and the cleavage occurs only under the
action of lysosomal proteolytic enzyme.
Antibody molecule4.1
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4.2

9. Cytotoxic drug
Cytotoxic drugs are commonly used chemotherapeutic drugs in the clinic, and the main
toxic effect spectrum of ADC drugs is determined. Because it has been widely used in
the clinic, its toxicity characteristics are generally clear.
Linker
Antibody molecule4.1
04.Toxicity risk of ADC
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4.2
4.3

10. ADC molecule
Drug antibody ratio (drug:antibodyratio, DAR) could significantly affect the toxicity of
ADC drugs.
The current ADC drugs are generally a mixture of different DAR, and the heterogeneity
of DAR will lead to uncertainty of toxicity due to the inconsistency of toxicity caused by
different DAR.
Unexpected toxicity caused by changes in antibody structure.
Cytotoxic drug
Linker
Antibody molecule4.1
04.Toxicity risk of ADC
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4.2
4.3
4.4

11. hematopoietic system toxicity
hepatotoxicity and reproductive toxicity
skin toxicity
Common toxicity of ADC drugs
4.5
nephrotoxicity
ADC molecule
Cytotoxic drug
Linker
Antibody molecule4.1
04.Toxicity risk of ADC
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4.2
4.3
4.4
4.5

12. Directional conjugation
By using directional coupling technique, the same number of drug
molecules can be carried on each antibody, and uniform ADC drugs
can be obtained, which is beneficial to the research and evaluation of
pharmacodynamics, and can get more stable and effective effect in the
clinical.
01
Multivalent conjugated ADC drugs
When site-specific modification is carried out, a variety of different
coupling groups can be designed, which can be used for drug coupling
of linker with corresponding groups. Finally, through the diversification
of linker to link a variety of drugs, to achieve multivalent coupling of
ADC drugs.
02
05.Development Trend
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13. Antibody identification and screening
01
linker and drug selection
02
Antibody-linker-drug coupling
03
ADC in vitro & in vivo analysis
04
antibody-antibiotic conjugate development services
05
06.About us
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14. Antibody-drug Conjugates
www.creative-biolabs.com/adc
Antiboby-drug Conjugate
45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-381-2994
Fax: 1-631-207-8356
Email: info@creative-biolabs.com