Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients
Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2015/285193 |
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| _version_ | 1832567594667737088 |
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| author | Ulka Vaishampayan Archana Thakur Ritesh Rathore Nicola Kouttab Lawrence G. Lum |
| author_facet | Ulka Vaishampayan Archana Thakur Ritesh Rathore Nicola Kouttab Lawrence G. Lum |
| author_sort | Ulka Vaishampayan |
| collection | DOAJ |
| description | Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 109 aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC. |
| format | Article |
| id | doaj-art-802faa0de7d14820af54808ac6cef89a |
| institution | Kabale University |
| issn | 2090-3111 2090-312X |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Prostate Cancer |
| spelling | doaj-art-802faa0de7d14820af54808ac6cef89a2025-02-03T01:01:03ZengWileyProstate Cancer2090-31112090-312X2015-01-01201510.1155/2015/285193285193Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer PatientsUlka Vaishampayan0Archana Thakur1Ritesh Rathore2Nicola Kouttab3Lawrence G. Lum4Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USADepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USARoger Williams Medical Center, Providence, RI 02908, USADepartment of Pathology, Roger Williams Medical Center, Providence, RI 02908, USADepartment of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USABackground. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 109 aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC.http://dx.doi.org/10.1155/2015/285193 |
| spellingShingle | Ulka Vaishampayan Archana Thakur Ritesh Rathore Nicola Kouttab Lawrence G. Lum Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients Prostate Cancer |
| title | Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients |
| title_full | Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients |
| title_fullStr | Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients |
| title_full_unstemmed | Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients |
| title_short | Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients |
| title_sort | phase i study of anti cd3 x anti her2 bispecific antibody in metastatic castrate resistant prostate cancer patients |
| url | http://dx.doi.org/10.1155/2015/285193 |
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