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Pasotuxizumab (BAY 2010112) is a PSMA and CD3 bispecific T-cell engager (BiTE). Pasotuxizumab binds to CD3 and PSMA with KDs of 9.4 nM and 47.0 nM for human CD3 and PSMA. Pasotuxizumab can be used for research of metastatic castration-resistant prostate cancer (mCRPC)[1][2]. | [in vivo]
Pasotuxizumab (0-100 ng/mL approximately, 48 h) leads to activation of CD4+ and CD8+ T cell populations, with EC50s of 3.4-6.7 ng/mL for human cocultures, and 13.7-21.2 ng/mL for cynomolgus monkey cell cocultures[2].
Pasotuxizumab (0-100 ng/mL approximately, 48 h) increases release of interferon-γ, TNF-α, IL-2 and IL-10 in T cells[2].
| Animal Model: | PC-3-huPSMA mouse xenograft model[2] | | Dosage: | 0.005-5 mg/kg | | Administration: | i.v., once daily | | Result: | Inhibited tumor growth by 86% (0.005 mg/kg/d) and 99% (5 mg/kg/d). |
| Animal Model: | BALB/c mice (PK Assay)[2] | | Dosage: | 0.1, 0.3, and 1 mg/kg | | Administration: | i.v. bolus administration or s.c. | | Result: | Pharmacokinetic profile of Rafivirumab.
| Dose (mg/kg) | AUC (mg h/L) | CLmatrix (L/h/kg) | T1/2 (h) | F (%) | |
| i.v. (0.3) | 0.93 | 0.32 | 9.7 | 100 | |
| s.c. (0.3) | 0.17 | | 11 | 18 |
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| [References]
[1] Horst-Dieter Hummel, et al. Phase 1 study of pasotuxizumab (BAY 2010112), a PSMA-targeting Bispecific T cell Engager (BiTE) immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology 2019 37:15_suppl, 5034-5034.
[2] Friedrich M, et al. Regression of human prostate cancer xenografts in mice by AMG 212/BAY2010112, a novel PSMA/CD3-Bispecific BiTE antibody cross-reactive with non-human primate antigens. Mol Cancer Ther. 2012 Dec;11(12):2664-73. DOI:10.1158/1535-7163.MCT-12-0042 |
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