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

302 Citations (Scopus)

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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Adaptive Immunity
Therapeutic Uses
Innate Immunity
Antibodies
Immunity
Neoplasm Antibodies
Neoplasms
Tumor Microenvironment
Tumor Burden
Immunotherapy
Therapeutics
T-Lymphocytes
Recurrence
Pharmaceutical Preparations

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., ... 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

The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. / Park, Sae Gwang; Jiang, Zhujun; Mortenson, Eric D.; Deng, Liufu; Radkevich-Brown, Olga; Yang, Xuanming; Sattar, Husain; Wang, Yang; Brown, Nicholas K.; Greene, Mark; Liu, Yang; Tang, Jie; Wang, Shengdian; Fu, Yang Xin.

In: Cancer Cell, Vol. 18, No. 2, 01.08.2010, p. 160-170.

Research output: Contribution to journalArticle

Park, SG, Jiang, Z, Mortenson, ED, Deng, L, Radkevich-Brown, O, Yang, X, Sattar, H, Wang, Y, Brown, NK, Greene, M, Liu, Y, Tang, J, Wang, S & Fu, YX 2010, 'The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity', Cancer Cell, vol. 18, no. 2, pp. 160-170. https://doi.org/10.1016/j.ccr.2010.06.014
Park SG, Jiang Z, Mortenson ED, Deng L, Radkevich-Brown O, Yang X et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell. 2010 Aug 1;18(2):160-170. https://doi.org/10.1016/j.ccr.2010.06.014
Park, Sae Gwang ; Jiang, Zhujun ; Mortenson, Eric D. ; Deng, Liufu ; Radkevich-Brown, Olga ; Yang, Xuanming ; Sattar, Husain ; Wang, Yang ; Brown, Nicholas K. ; Greene, Mark ; Liu, Yang ; Tang, Jie ; Wang, Shengdian ; Fu, Yang Xin. / The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. In: Cancer Cell. 2010 ; Vol. 18, No. 2. pp. 160-170.
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