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Anetumab ravtansine (BAY 94-9343) is a selective and highly potent antibody-drug conjugate (ADC) to target maytansinoid tubulin. Anetumab ravtansine consists of a human anti-mesothelin antibody conjugated to the maytansinoid tubulin inhibitor DM4. Anetumab ravtansine shows antitumor efficacy correlated with the amount of mesothelin expressed in patient-derived xenograft tumor models[1]. | [in vivo]
Anetumab ravtansine (10 mg/kg; i.v.) is localized specifically to mesothelin-positive tumors and inhibits tumor growth in both subcutaneous and orthotopic xenograft models[1].
| Animal Model: | Subcutaneous and orthotopic xenograft models: MIA PaCa, HT29, OVCAR-3, NCI-H226 and so on (NMRI nu/nu mice: 18-25 g, 7-10 weeks old)[1] | | Dosage: | 2.7 mg/kg (0.05 mg/kg DM4), 10.6 mg/kg (0.2 mg/kg DM4) | | Administration: | MF-T, or S-methyl-DM4 on days 5, 8, and 12 (mice implanted with MIA PaCa or HT29 meso cells); on days 33, 36, and 40 (OVCAR-3); on days 78, 81, 84, 127, 130, and 133 (NCI-H226); on days 15, 18, and 22 (OVCAR-3- s-05 orthotopic); on days 7, 10, and 13 (HT29 titration); Q3Dx3 starting on day 0 (PAXF736); Q3Dx3 starting on day 29 (OVCAR6719); or Q4Dx3 starting on day 34 (Meso7212) after tumor cell inoculation. | | Result: | Resulted in complete tumor eradication at 10.6 mg/kg (0.2 mg/kg DM4), lasting for at least 17 weeks following the final treatment.
Eradicated tumors in 5 out of 6 animals in the MIA PaCa-2/meso model rather than in HT-29/ meso model at 2.7 mg/kg (0.05 mg/kg DM4).
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| [References]
[1] Golfier S, et al. Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect. Mol Cancer Ther. 2014 Jun;13(6):1537-48. DOI:10.1158/1535-7163.MCT-13-0926 |
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