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Prostate Cancer
Volume 2015, Article ID 285193, 10 pages
http://dx.doi.org/10.1155/2015/285193
Clinical Study

Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients

1Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA
2Department of Medicine, Wayne State University, Detroit, MI 48201, USA
3Roger Williams Medical Center, Providence, RI 02908, USA
4Department of Pathology, Roger Williams Medical Center, Providence, RI 02908, USA
5Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201, USA

Received 10 November 2014; Revised 9 January 2015; Accepted 15 January 2015

Academic Editor: Hendrik Van Poppel

Copyright © 2015 Ulka Vaishampayan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 × 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.