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
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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.
Cancer cell 08/2010; 18(2):160-70. · 25.29 Impact Factor
