Effects of a human compact anti-ErbB2 antibody on prostate cancer.

Abstract

Prostate cancer is the most commonly diagnosed malignancy in men in developed countries. ErbB2, a tyrosine kinase receptor overexpressed in many human cancer types, contributes to prostate cancer progression by activating the androgen receptor in a steroid poor environment, thus promoting androgen-independent cell growth. The consequent development of hormone refractory tumors is a major obstacle in prostate cancer therapy. The inhibition of ErbB2 signal transduction pathways by the use of human antibodies could be a valuable alternative strategy for cancer therapy. We performed a comparative analysis in vitro and in vivo of the antitumor effects of three different antibodies targeting different epitopes of ErbB2: Herceptin (trastuzumab), 2C4 (pertuzumab) and Erb-hcAb (human anti-ErbB2-compact antibody), a novel fully human compact antibody produced in our laboratory. Herein, we demonstrate that the growth of both androgen-dependent and independent prostate cancer cells was efficiently inhibited by Erb-hcAb. The antitumor effects induced by Erb-hcAb on some cell lines were more potent than those observed for either Herceptin or 2C4. Thus, Erb-hcAb could be a promising candidate in the immunotherapy of prostate cancer for which no obvious treatment has been reported so far.

• Authors: Angela Eliana Malara, Carmine Fedele, Luigi Aloj, Claudio Arra, Paolo Laccetti, Giuseppe D'Alessio, Claudia De Lorenzo
• Journal: Oncology reports (Oncol Rep) Vol. 28 Issue 1 Pg. 297-302 (Jul 2012) ISSN: 1791-2431 [Electronic] Greece
• PMID: 22505344 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2C4 antibody
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Recombinant Fusion Proteins
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Animals
• Antibodies, Monoclonal (metabolism, pharmacology)
• Antibodies, Monoclonal, Humanized (metabolism, pharmacokinetics, pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacokinetics, pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Half-Life
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Prostatic Neoplasms (drug therapy, metabolism)
• Protein Binding
• Receptor, ErbB-2 (metabolism)
• Recombinant Fusion Proteins (pharmacokinetics, pharmacology, therapeutic use)
• Tissue Distribution
• Trastuzumab
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays