The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity.
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.
Park
SaeGwang
S
Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing, China.
Jiang
Zhujun
Z
Mortenson
Eric D
ED
Deng
Liufu
L
Radkevich-Brown
Olga
O
Yang
Xuanming
X
Sattar
Husain
H
Wang
Yang
Y
Brown
Nicholas K
NK
Greene
Mark
M
Liu
Yang
Y
Tang
Jie
J
Wang
Shengdian
S
Fu
Yang-Xin
YX
D056704:Adaptive Immunity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human