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Antitumor vaccination with HER‐2‐derived recombinant antigens
Author(s) -
Vidovic Damir,
Graddis Thomas,
Chen Feng,
Slagle Paul,
Diegel Michael,
Stepan Lara,
Laus Reiner
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10785
Subject(s) - internalization , antigen , fusion protein , immunotherapy , biology , antigen presentation , tyrosine kinase , transmembrane protein , in vitro , glycoprotein , receptor , cancer research , recombinant dna , immunology , microbiology and biotechnology , t cell , immune system , signal transduction , biochemistry , gene
Certain types of malignant tumors overexpress HER‐2, a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family. To develop an effective HER‐2 vaccine for the selective immunotherapy of these malignancies, we have genetically engineered fusion proteins containing portions of extra‐ and intracellular HER‐2 domains. Activated dendritic cells (DC) cocultured with these novel antigens (Ag) could induce potent responses of Ag‐specific T‐cell lines in vitro and a protection against HER‐2‐expressing tumor in vivo . The protective capabilities of HER‐2‐derived fusion proteins correlated with the efficiency of their presentation to Ag‐specific T‐cell hybridomas. The most effective Ag contained GM‐CSF, the presence of which facilitated their internalization by antigen‐presenting cells (APC) in a receptor‐mediated manner. © 2002 Wiley‐Liss, Inc.