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Lentiviral vector followed by protein immunisation breaks tolerance against the self‐antigen Her1 and results in lung cancer immunotherapy
Author(s) -
Alpizar Yeranddy Aguiar,
Karwacz Katarzyna,
Arce Frederick,
Rivera Arianna Yglesias,
Fernández Luis Enrique,
Collins Mary K.,
Ramírez Belinda Sánchez
Publication year - 2012
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.2606
Subject(s) - lung cancer , antigen , antibody , cd8 , immunotherapy , immunology , priming (agriculture) , cytotoxic t cell , viral vector , cancer immunotherapy , cancer , medicine , cancer research , biology , virology , immune system , oncology , gene , genetics , germination , botany , in vitro , recombinant dna
Background Lung cancer remains a leading cause of cancer mortality, and so the aim of the present study was to develop a therapeutic vaccine protocol. Methods We constructed a lentiviral vector (LV) expressing the extracellular domain (ECD) of murine Her1, an antigen associated with poor prognosis in lung cancer. Results A single LV injection, followed by two Her1 protein boosts, was effective in reducing the metastatic burden of Lewis lung carcinoma in mice. The Her1 LV immunisation generated CD8+ T cells that recognised Her1 ECD presented by dendritic cells, and that also homed to Her1‐expressing tumours. Protein boosting further increased the CD8+ T cell response and generated anti‐Her1 antibodies; in the antibody response, Her1 LV priming increased Th1‐dependent immunoglobulin G2c production. Conclusions The ability of this vaccine protocol to break both T cell and B cell tolerance to a self‐antigen likely explains its effectiveness. Copyright © 2012 John Wiley & Sons, Ltd.