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

Cancer Cell. 2010 Aug 9;18(2):160-70. doi: 10.1016/j.ccr.2010.06.014.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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