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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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| Zeitschriftentitel: | Molecular Cancer Therapeutics |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , |
| In: | Molecular Cancer Therapeutics, 11, 2012, 12, S. 2664-2673 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
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 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 |
|---|---|
| author |
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 |
| spellingShingle |
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 Molecular Cancer Therapeutics 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 Cancer Research Oncology |
| author_sort |
friedrich, matthias |
| spelling |
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 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-12-0042 <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> 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 Molecular Cancer Therapeutics |
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10.1158/1535-7163.mct-12-0042 |
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American Association for Cancer Research (AACR), 2012 |
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Molecular Cancer Therapeutics |
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| title |
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 |
| title_unstemmed |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_short |
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 |
| title_sort |
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 |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1535-7163.mct-12-0042 |
| publishDate |
2012 |
| physical |
2664-2673 |
| description |
<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> |
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| author | 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 |
| author_facet | 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, 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 |
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| description | <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> |
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| spelling | 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 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-12-0042 <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> 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 Molecular Cancer Therapeutics |
| spellingShingle | 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, Molecular Cancer Therapeutics, 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, Cancer Research, Oncology |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| title_unstemmed | 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 |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1535-7163.mct-12-0042 |