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Open Access Green as soon as Postprint is submitted to ZB.
CTLs directed against HER2 specifically cross-react with HER3 and HER4.
J. Immunol. 180, 8135-8145 (2008)
The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated Ag by T cell-based immunotherapeutical strategies such as cancer vaccines and adoptive T cell transfer. The prerequisite for a successful T cell-based therapy is the induction of T cells capable of recognizing the HER2-expressing tumor cells. In this study, we generated human cytotoxic T cell clones directed against the HER2(369-377) epitope known to be naturally presented with HLA-A*0201. Those HER2-reactive CTLs, which were also tumor lytic, exhibited a similar lysis pattern dividing the targets in lysable and nonlysable tumor cells. Several HER2-expressing tumor cells became susceptible to CTL-mediated lysis after IFN-gamma treatment and, in parallel, up-regulated molecules of the Ag-presenting machinery, indicating that the tumor itself also contributes to the success of CTL-mediated killing. Some of the HER2(369-377)-reactive T cells specifically cross-reacted with the corresponding peptides derived from the family members HER3 and/or HER4 due to a high sequence homology. The epitopes HER3(356-364) and HER4(361-369) were endogenously processed and contributed to the susceptibility of cell lysis by HER cross-reacting CTLs. The principle of "double" or "triple targeting" the HER Ags by cross-reacting T cells will impact the further development of T cell-based therapies.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0022-1767
e-ISSN
1550-6606
Journal
Journal of Immunology
Quellenangaben
Volume: 180,
Issue: 12,
Pages: 8135-8145
Publisher
American Association of Immunologists
Reviewing status
Peer reviewed
Institute(s)
Institute of Virology (VIRO)