Antibody Conjugates-Recent Advances and Future Innovations
Abstract
:1. Introduction
2. Critical Considerations for Antibody Conjugates
2.1. Target and Antibody Selection
2.2. Conjugation Methods
3. Current Small Molecule Payloads and Beyond
4. Nucleic Acid Conjugates
5. Linkers
6. Absorption, Distribution, Metabolism, and Excretion (ADME) of ADCs
7. Conjugate Developability, Formulations, and Characteristics
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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ADC Product | Indications | Approval Date | Target Antigen | Antibody Conjugation | Average Drug Antibody Ratio (DAR) | Linker | Payload |
---|---|---|---|---|---|---|---|
Mylotarg® (Gemtuzumab ozogamicin) | Relapsed AML | 2001, withdrawn 2010; (reapproved 2017) | CD33 | Humanized IgG4—lysine | 2–3 | Hydrazone | Calicheamicin |
Adcetris® (Brentuximab vedotin) | Relapsed HL and sALCL | 2011 | CD30 | Chimeric IgG1—cysteine | ~4 | Dipeptide cleavable (Val-Cit) | Monomethyl auristatin E (MMAE) |
Kadcyla® (Trastuzumab emtansine) | HER2 + metastatic breast cancer | 2013 | HER2 | Humanized IgG1—lysine | 3.5 | Thioether Non-cleavable | Emtansine (DM1) |
Besponsa® (Inotuzumab ozogamicin) | Relapsed or refractory CD22 + B-ALL | 2017 | CD22 | Humanized IgG4—lysine | ~4 | Hydrazone | Calicheamicin |
Polivy® (Polatuzumab vedotin) | Relapsed or refractory DLBCL | 2019 | CD79b | Humanized IgG1—cysteine | 3.5 | Dipeptide cleavable (Val-Cit) | Monomethyl auristatin E (MMAE) |
Enhertu® (fam-trastuzumab deruxtecan-nxki) | HER2 + unresectable metastic breast cancer | 2019 | HER2 | Humanized IgG1—cysteine | 7–8 | Tetrapeptide cleavable (Gly-gly-Phe-Gly) | Exatecan derivative (Dxd) |
Species | ADME Information |
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Leung, D.; Wurst, J.M.; Liu, T.; Martinez, R.M.; Datta-Mannan, A.; Feng, Y. Antibody Conjugates-Recent Advances and Future Innovations. Antibodies 2020, 9, 2. https://doi.org/10.3390/antib9010002
Leung D, Wurst JM, Liu T, Martinez RM, Datta-Mannan A, Feng Y. Antibody Conjugates-Recent Advances and Future Innovations. Antibodies. 2020; 9(1):2. https://doi.org/10.3390/antib9010002
Chicago/Turabian StyleLeung, Donmienne, Jacqueline M. Wurst, Tao Liu, Ruben M. Martinez, Amita Datta-Mannan, and Yiqing Feng. 2020. "Antibody Conjugates-Recent Advances and Future Innovations" Antibodies 9, no. 1: 2. https://doi.org/10.3390/antib9010002
APA StyleLeung, D., Wurst, J. M., Liu, T., Martinez, R. M., Datta-Mannan, A., & Feng, Y. (2020). Antibody Conjugates-Recent Advances and Future Innovations. Antibodies, 9(1), 2. https://doi.org/10.3390/antib9010002