title: Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients.
abstract: 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 × 10(9) 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.
authors: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA ; Department of Medicine, Wayne State University, Detroit, MI 48201, USA.
authors: Ulka
authors: 0000-0001-5800-4571
authors: U
authors: Vaishampayan
authors: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA.
authors: Archana
authors: A
authors: Thakur
authors: Roger Williams Medical Center, Providence, RI 02908, USA.
authors: Ritesh
authors: R
authors: Rathore
authors: Department of Pathology, Roger Williams Medical Center, Providence, RI 02908, USA.
authors: Nicola
authors: N
authors: Kouttab
authors: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA ; Department of Medicine, Wayne State University, Detroit, MI 48201, USA ; Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201, USA.
authors: Lawrence G
authors: LG
authors: Lum