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

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Bibliographische Detailangaben
Zeitschriftentitel:	Molecular Cancer Therapeutics
Personen und Körperschaften:	Friedrich, Matthias, Raum, Tobias, Lutterbuese, Ralf, Voelkel, Markus, Deegen, Petra, Rau, Doris, Kischel, Roman, Hoffmann, Patrick, Brandl, Christian, Schuhmacher, Joachim, Mueller, Peter, Finnern, Ricarda, Fuergut, Melanie, Zopf, Dieter, Slootstra, Jerry W., Baeuerle, Patrick A., Rattel, Benno, Kufer, Peter
In:	Molecular Cancer Therapeutics, 11, 2012, 12, S. 2664-2673
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	American Association for Cancer Research (AACR)
Schlagwörter:	Cancer Research Oncology

Details
Zusammenfassung:	<jats:title>Abstract</jats:title> <jats:p>For treatment of patients with prostate cancer (PCa), we developed a novel T cell-engaging (BiTE) antibody designated AMG 212 or BAY2010112 that is bispecific for prostate-specific membrane antigen (PSMA) and the CD3 epsilon subunit of the T cell receptor complex. AMG 212/BAY2010112 induced target cell-dependent activation and cytokine release of T cells, and efficiently redirected T cells for lysis of target cells. In addition to Chinese hamster ovary cells stably expressing human or cynomolgus monkey PSMA, T cells redirected by AMG 212/BAY2010112 also lysed human PCa cell lines VCaP, 22Rv1, MDA PCa 2b, C4-2, PC-3-huPSMA, and LnCaP at half maximal BiTE concentrations between 0.1 and 4 ng/mL (1.8–72 pmol/L). No lysis of PSMA-negative human PCa cell lines PC-3 and DU145 was observed. The subcutaneous (s.c.) formation of tumors from PC-3-huPSMA cells in NOD/SCID mice was significantly prevented by once daily intravenous (i.v.) injection of AMG 212/BAY2010112 at a dose level as low as 0.005 mg/kg/d. Rapid tumor shrinkage with complete remissions were observed in NOD/SCID mice bearing established s.c. 22Rv1 xenografts after repeated daily treatment with AMG 212/BAY2010112 by either the i.v. or s.c. route. Of note, 22Rv1 tumors were grown in the absence of human T cells followed by intraperitoneal injection of T cells 3 days before BiTE treatment. No effects on tumor growth were observed in the absence of human T cells or AMG 212/BAY2010112. On the basis of these preclinical results, AMG 212/BAY2010112 appears as a promising new BiTE antibody for the treatment of patients with PSMA-expressing PCa. Mol Cancer Ther; 11(12); 2664–73. ©2012 AACR.</jats:p>
Umfang:	2664-2673
ISSN:	1535-7163 1538-8514
DOI:	10.1158/1535-7163.mct-12-0042