The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity.

Abstract

Anti-HER2/neu antibody therapy is reported to mediate tumor regression by interrupting oncogenic signals and/or inducing FcR-mediated cytotoxicity. Here, we demonstrate that the mechanisms of tumor regression by this therapy also require the adaptive immune response. Activation of innate immunity and T cells, initiated by antibody treatment, was necessary. Intriguingly, the addition of chemotherapeutic drugs, although capable of enhancing the reduction of tumor burden, could abrogate antibody-initiated immunity leading to decreased resistance to rechallenge or earlier relapse. Increased influx of both innate and adaptive immune cells into the tumor microenvironment by a selected immunotherapy further enhanced subsequent antibody-induced immunity, leading to increased tumor eradication and resistance to rechallenge. This study proposes a model and strategy for anti-HER2/neu antibody-mediated tumor clearance.

• Authors: SaeGwang Park, Zhujun Jiang, Eric D Mortenson, Liufu Deng, Olga Radkevich-Brown, Xuanming Yang, Husain Sattar, Yang Wang, Nicholas K Brown, Mark Greene, Yang Liu, Jie Tang, Shengdian Wang, Yang-Xin Fu
• Journal: Cancer cell (Cancer Cell) Vol. 18 Issue 2 Pg. 160-70 (Aug 09 2010) ISSN: 1878-3686 [Electronic] United States
• PMID: 20708157 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adaptive Immunity
• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Humans
• Immunity, Innate
• Immunologic Memory
• Male
• Mice
• Mice, Inbred BALB C
• Receptor, ErbB-2 (immunology)
• T-Lymphocytes, Cytotoxic (immunology)