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

Sae Gwang 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

Research output: Contribution to journalArticle

312 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)160-170
Number of pages11
JournalCancer Cell
Volume18
Issue number2
DOIs
StatePublished - Aug 1 2010

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Keywords

  • Cellcycle
  • Cellimmuno
  • Molimmuno

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Park, S. G., Jiang, Z., Mortenson, E. D., Deng, L., Radkevich-Brown, O., Yang, X., Sattar, H., Wang, Y., Brown, N. K., Greene, M., Liu, Y., Tang, J., Wang, S., & Fu, Y. X. (2010). The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell, 18(2), 160-170. https://doi.org/10.1016/j.ccr.2010.06.014