| Linker-payload . | Type . | ADC . | Estimation of antibody-linker instability in circulationa [2] . | Estimation of linker-payload instability in circulationb [2] . | ADC in vitro stability (plasma) . | ADC in vitro stability (buffer) . |
|---|---|---|---|---|---|---|
| Ozogamicin | Cleavable | Mylotarg® Besponsa® | / | Plasma 7 days: 20% remaining | Low plasma stability [54] | pH 4.5, 37°C 24 hrs: 97% hydrolysis [65] pH 7.4, 37°C 24 hrs: 6% hydrolysis |
| Vedotin | Cleavable | Adcetris® Polivy® Padcev® Aidixi® Tivdak® | Plasma 7 days: 50% remaining | / | Plasma 10 days: 2% free drug release [66] | Adcetris® (CS: DAR 3.5, Free drug 0.3 μg/mlc) [67] pH 4.0, 37°C 4 weeks: DAR 1.3, Free drug 110 μg/mlc pH 6.0, 37°C 4 weeks: DAR 3.2 pH 8.0, 37°C 4 weeks: DAR 2.2 pH 10.0, 37°C 4 weeks: DAR 2.1, Free drug 70 μg/mlc |
| Emtansine | Non-Cleavable | Kadcyla® | / | Plasma 7 days: 50% remaining | Plasma 4 days: 70% remaining [68] | Kadcyla® (CS: 0.47% free maytansinoid) [69] pH 4.0, 37°C 4 weeks: 2.4% free maytansinoid pH 10.0, 37°C 4 weeks: 6.1% free maytansinoid |
| Deruxtecan | Cleavable | Enhertu® | Plasma 7 days: 50% remaining | / | Plasma 21 days: 2.1% free drug release [70] | PB with 1% BSA, 37°C 21 days: 0.2% free drug release, comparable or rather lower than Kadcyla® and Adcetris® [70] |
| Govitecan | Cleavable | Trodelvy® | Plasma 7 days: 50% remaining | Plasma 7 days: 50% remaining | Plasma 36 hrs: 50% free drug release [71] | pH 5.3, 37°C 13 hrs: 50% SN-38 release pH 7.4, 37°C 30 hrs: 50% SN-38 release [37] |
| Tirumotecan | Cleavable | sac-TMT® | / | Plasma 7 days: 50% remaining | Plasma 144 hrs: 70% free drug release [72] | No formulation stability data is disclosed. |
| Tesirine | Cleavable | Zynlonta® | Plasma 7 days: 80% remaining | / | Stable in plasma [73] | pH 7.8, 37°C 3 days: decrease (~0.11 units) of isoelectric point [74] |
| Soravtansine | Cleavable | Elahere® | / | Plasma 7 days: 40% remaining | Stable in plasma [75] | Soluble in neutral buffer and stable for up to 2 years upon storage at 4°C [76] |
| Linker-payload . | Type . | ADC . | Estimation of antibody-linker instability in circulationa [2] . | Estimation of linker-payload instability in circulationb [2] . | ADC in vitro stability (plasma) . | ADC in vitro stability (buffer) . |
|---|---|---|---|---|---|---|
| Ozogamicin | Cleavable | Mylotarg® Besponsa® | / | Plasma 7 days: 20% remaining | Low plasma stability [54] | pH 4.5, 37°C 24 hrs: 97% hydrolysis [65] pH 7.4, 37°C 24 hrs: 6% hydrolysis |
| Vedotin | Cleavable | Adcetris® Polivy® Padcev® Aidixi® Tivdak® | Plasma 7 days: 50% remaining | / | Plasma 10 days: 2% free drug release [66] | Adcetris® (CS: DAR 3.5, Free drug 0.3 μg/mlc) [67] pH 4.0, 37°C 4 weeks: DAR 1.3, Free drug 110 μg/mlc pH 6.0, 37°C 4 weeks: DAR 3.2 pH 8.0, 37°C 4 weeks: DAR 2.2 pH 10.0, 37°C 4 weeks: DAR 2.1, Free drug 70 μg/mlc |
| Emtansine | Non-Cleavable | Kadcyla® | / | Plasma 7 days: 50% remaining | Plasma 4 days: 70% remaining [68] | Kadcyla® (CS: 0.47% free maytansinoid) [69] pH 4.0, 37°C 4 weeks: 2.4% free maytansinoid pH 10.0, 37°C 4 weeks: 6.1% free maytansinoid |
| Deruxtecan | Cleavable | Enhertu® | Plasma 7 days: 50% remaining | / | Plasma 21 days: 2.1% free drug release [70] | PB with 1% BSA, 37°C 21 days: 0.2% free drug release, comparable or rather lower than Kadcyla® and Adcetris® [70] |
| Govitecan | Cleavable | Trodelvy® | Plasma 7 days: 50% remaining | Plasma 7 days: 50% remaining | Plasma 36 hrs: 50% free drug release [71] | pH 5.3, 37°C 13 hrs: 50% SN-38 release pH 7.4, 37°C 30 hrs: 50% SN-38 release [37] |
| Tirumotecan | Cleavable | sac-TMT® | / | Plasma 7 days: 50% remaining | Plasma 144 hrs: 70% free drug release [72] | No formulation stability data is disclosed. |
| Tesirine | Cleavable | Zynlonta® | Plasma 7 days: 80% remaining | / | Stable in plasma [73] | pH 7.8, 37°C 3 days: decrease (~0.11 units) of isoelectric point [74] |
| Soravtansine | Cleavable | Elahere® | / | Plasma 7 days: 40% remaining | Stable in plasma [75] | Soluble in neutral buffer and stable for up to 2 years upon storage at 4°C [76] |
a Antibody-linker instability in circulation refers to the whole linker-drug release from the antibody, such as the retro-Michael reaction for thiol–maleimide conjugation.
b Linker-payload instability in circulation refers to the drug release over time prior to its intended site of metabolism.
c Free drug includes MMAE, NACvcMMAE and other unknown free drugs.
Abbreviation: CS, control sample.
Note: Blenrep® and Lumoxiti® were withdrawn from markets. Akalux® employs a unique linker system distinct from conventional ADCs. These three ADCs are excluded from Table 3.
| Linker-payload . | Type . | ADC . | Estimation of antibody-linker instability in circulationa [2] . | Estimation of linker-payload instability in circulationb [2] . | ADC in vitro stability (plasma) . | ADC in vitro stability (buffer) . |
|---|---|---|---|---|---|---|
| Ozogamicin | Cleavable | Mylotarg® Besponsa® | / | Plasma 7 days: 20% remaining | Low plasma stability [54] | pH 4.5, 37°C 24 hrs: 97% hydrolysis [65] pH 7.4, 37°C 24 hrs: 6% hydrolysis |
| Vedotin | Cleavable | Adcetris® Polivy® Padcev® Aidixi® Tivdak® | Plasma 7 days: 50% remaining | / | Plasma 10 days: 2% free drug release [66] | Adcetris® (CS: DAR 3.5, Free drug 0.3 μg/mlc) [67] pH 4.0, 37°C 4 weeks: DAR 1.3, Free drug 110 μg/mlc pH 6.0, 37°C 4 weeks: DAR 3.2 pH 8.0, 37°C 4 weeks: DAR 2.2 pH 10.0, 37°C 4 weeks: DAR 2.1, Free drug 70 μg/mlc |
| Emtansine | Non-Cleavable | Kadcyla® | / | Plasma 7 days: 50% remaining | Plasma 4 days: 70% remaining [68] | Kadcyla® (CS: 0.47% free maytansinoid) [69] pH 4.0, 37°C 4 weeks: 2.4% free maytansinoid pH 10.0, 37°C 4 weeks: 6.1% free maytansinoid |
| Deruxtecan | Cleavable | Enhertu® | Plasma 7 days: 50% remaining | / | Plasma 21 days: 2.1% free drug release [70] | PB with 1% BSA, 37°C 21 days: 0.2% free drug release, comparable or rather lower than Kadcyla® and Adcetris® [70] |
| Govitecan | Cleavable | Trodelvy® | Plasma 7 days: 50% remaining | Plasma 7 days: 50% remaining | Plasma 36 hrs: 50% free drug release [71] | pH 5.3, 37°C 13 hrs: 50% SN-38 release pH 7.4, 37°C 30 hrs: 50% SN-38 release [37] |
| Tirumotecan | Cleavable | sac-TMT® | / | Plasma 7 days: 50% remaining | Plasma 144 hrs: 70% free drug release [72] | No formulation stability data is disclosed. |
| Tesirine | Cleavable | Zynlonta® | Plasma 7 days: 80% remaining | / | Stable in plasma [73] | pH 7.8, 37°C 3 days: decrease (~0.11 units) of isoelectric point [74] |
| Soravtansine | Cleavable | Elahere® | / | Plasma 7 days: 40% remaining | Stable in plasma [75] | Soluble in neutral buffer and stable for up to 2 years upon storage at 4°C [76] |
| Linker-payload . | Type . | ADC . | Estimation of antibody-linker instability in circulationa [2] . | Estimation of linker-payload instability in circulationb [2] . | ADC in vitro stability (plasma) . | ADC in vitro stability (buffer) . |
|---|---|---|---|---|---|---|
| Ozogamicin | Cleavable | Mylotarg® Besponsa® | / | Plasma 7 days: 20% remaining | Low plasma stability [54] | pH 4.5, 37°C 24 hrs: 97% hydrolysis [65] pH 7.4, 37°C 24 hrs: 6% hydrolysis |
| Vedotin | Cleavable | Adcetris® Polivy® Padcev® Aidixi® Tivdak® | Plasma 7 days: 50% remaining | / | Plasma 10 days: 2% free drug release [66] | Adcetris® (CS: DAR 3.5, Free drug 0.3 μg/mlc) [67] pH 4.0, 37°C 4 weeks: DAR 1.3, Free drug 110 μg/mlc pH 6.0, 37°C 4 weeks: DAR 3.2 pH 8.0, 37°C 4 weeks: DAR 2.2 pH 10.0, 37°C 4 weeks: DAR 2.1, Free drug 70 μg/mlc |
| Emtansine | Non-Cleavable | Kadcyla® | / | Plasma 7 days: 50% remaining | Plasma 4 days: 70% remaining [68] | Kadcyla® (CS: 0.47% free maytansinoid) [69] pH 4.0, 37°C 4 weeks: 2.4% free maytansinoid pH 10.0, 37°C 4 weeks: 6.1% free maytansinoid |
| Deruxtecan | Cleavable | Enhertu® | Plasma 7 days: 50% remaining | / | Plasma 21 days: 2.1% free drug release [70] | PB with 1% BSA, 37°C 21 days: 0.2% free drug release, comparable or rather lower than Kadcyla® and Adcetris® [70] |
| Govitecan | Cleavable | Trodelvy® | Plasma 7 days: 50% remaining | Plasma 7 days: 50% remaining | Plasma 36 hrs: 50% free drug release [71] | pH 5.3, 37°C 13 hrs: 50% SN-38 release pH 7.4, 37°C 30 hrs: 50% SN-38 release [37] |
| Tirumotecan | Cleavable | sac-TMT® | / | Plasma 7 days: 50% remaining | Plasma 144 hrs: 70% free drug release [72] | No formulation stability data is disclosed. |
| Tesirine | Cleavable | Zynlonta® | Plasma 7 days: 80% remaining | / | Stable in plasma [73] | pH 7.8, 37°C 3 days: decrease (~0.11 units) of isoelectric point [74] |
| Soravtansine | Cleavable | Elahere® | / | Plasma 7 days: 40% remaining | Stable in plasma [75] | Soluble in neutral buffer and stable for up to 2 years upon storage at 4°C [76] |
a Antibody-linker instability in circulation refers to the whole linker-drug release from the antibody, such as the retro-Michael reaction for thiol–maleimide conjugation.
b Linker-payload instability in circulation refers to the drug release over time prior to its intended site of metabolism.
c Free drug includes MMAE, NACvcMMAE and other unknown free drugs.
Abbreviation: CS, control sample.
Note: Blenrep® and Lumoxiti® were withdrawn from markets. Akalux® employs a unique linker system distinct from conventional ADCs. These three ADCs are excluded from Table 3.
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