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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/10508

Title: Identification and characterization of ErbB-3-binding protein-1 as a target for immunotherapy
Authors: Santegoets, Saskia J. A. M.
Schreurs, Marco W. J.
Reurs, Anneke W.
Lindenberg, Jelle J.
Kueter, Esther W. M.
van den Eertwegh, Alfons J. M.
Hooijberg, Erik
Brandwijk, Ricardo J.
Hufton, Simon E.
Hoogenboom, Hennie R.
Scheper, Rik J.
SOMERS, Veerle
de Gruijl, Tanja D.
Issue Date: 2007
Publisher: AMER ASSOC IMMUNOLOGISTS
Citation: JOURNAL OF IMMUNOLOGY, 179(3). p. 2005-2012
Abstract: Based on immune reactivity in response to a whole-cell colon tumor vaccine and using serological identification of Ags by recombinant cDNA expression cloning, we here describe the molecular and functional identification of a novel human tumor Ag. By screening a cDNA expression library derived from the coloncarcinoma cell line HT-29 with pooled colorectal cancer patients sera, 26 clones reactive with IgG Abs could be identified. Characterization of these cDNA clones by sequence analysis and alignment, and detailed serological analysis revealed cancer-related immunoreactivity for the ErbB-3-binding protein-1 (Ebp1). Immunohistochemical staining of colorectal tumors and neighboring normal colon tissue indicated the observed cancer-related immunogenicity of Ebp1 to be related to overexpression. Via reverse immunology, five potential HLA-A2-restricted T cell epitopes were identified, of which two (Ebp1(45-54) and Ebp1(59-67)) bound HLA-A2 with intermediate and high affinity, respectively. Analysis of their immunogenicity in vitro indicated that only the high-affinity Ebp1(59) epitope gave rise to CD8(+) T cells capable of recognizing both exogenously loaded Ebp1 peptide and endogenously expressed Ebp1 on target cells. In addition, in vivo CD8(+) T cell responsiveness against the Ebp1(59) epitope could be detected in two of nine and three of six cancer patients PBMC and tumor draining lymph nodes, respectively, but not in nine of nine healthy donors tested. These data confirm that Ebp1 is an immunogenic protein, capable of eliciting CD8-mediated responses in vivo and in vitro, providing a rationale for further exploration of Ebp1 as a possible target for anticancer immunotherapy.
Notes: Vrije Univ Amsterdam, Dept Pathol, Amsterdam, Netherlands. Vrije Univ Amsterdam, Dept Med Oncol, Amsterdam, Netherlands. Maastricht Univ, Dept Pathol, Maastricht, Netherlands.
URI: http://hdl.handle.net/1942/10508
Link to publication: http://www.jimmunol.org/cgi/content/abstract/179/3/2005
ISI #: 000248319700065
ISSN: 0022-1767
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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