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Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes

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Hofmann, Uta B ; Voigt, Heike ; Andersen, Mads H ; Straten, Per Thor ; Becker, Jürgen C ; Eggert, Andreas O. / Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes. In: European Journal of Immunology. 2009 ; Vol. 39, No. 5. pp. 1419-24.

Bibtex

@article{fc7c2174b0814e25a3008d23632f9159,
title = "Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes",
abstract = "Survivin is overexpressed in several malignancies and in tumor-associated endothelium making it an attractive target for therapeutic cytotoxic T-cell responses. Thus, it would be important to test this notion in preclinical models. Consequently, we screened the murine survivin sequence for potential binding K(b)-restricted octamer peptide epitopes. Two epitopes, which bind strongly to K(b), were selected to test their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature DC pulsed with these peptides displayed reactivity to the respective epitopes. The natural processing and presentation of these epitopes by tumor cells was evident by the killing of murine melanoma cells by vaccination-induced T cells. Subcutaneous challenge with syngeneic melanoma demonstrated the protective immunity of this vaccination. Notably, analysis of the vessel density in subcutaneous tumors revealed that survivin-specific vaccination significantly reduced the number of intratumoral vessels. In summary, we demonstrated the immunogenicity of two K(b)-restricted peptide epitopes derived from the murine survivin protein; moreover, survivin-specific vaccination not only resulted in a reduction of tumor cells but also the tumor supplying blood vessels. The presented preclinical model for survivin-directed vaccination may serve as a valuable tool to improve already running clinical trials in a syngeneic tumor model.",
keywords = "Animals, Cancer Vaccines, Cell Line, Tumor, Enzyme-Linked Immunosorbent Assay, Epitopes, T-Lymphocyte, Female, H-2 Antigens, Humans, Immunohistochemistry, Immunotherapy, Inhibitor of Apoptosis Proteins, Melanoma, Mice, Mice, Inbred C57BL, Microtubule-Associated Proteins, Neovascularization, Pathologic, Repressor Proteins, T-Lymphocytes, Cytotoxic, Journal Article, Research Support, Non-U.S. Gov't",
author = "Hofmann, {Uta B} and Heike Voigt and Andersen, {Mads H} and Straten, {Per Thor} and Becker, {J{\"u}rgen C} and Eggert, {Andreas O}",
year = "2009",
month = may,
doi = "10.1002/eji.200839098",
language = "English",
volume = "39",
pages = "1419--24",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "5",

}

RIS

TY - JOUR

T1 - Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes

AU - Hofmann, Uta B

AU - Voigt, Heike

AU - Andersen, Mads H

AU - Straten, Per Thor

AU - Becker, Jürgen C

AU - Eggert, Andreas O

PY - 2009/5

Y1 - 2009/5

N2 - Survivin is overexpressed in several malignancies and in tumor-associated endothelium making it an attractive target for therapeutic cytotoxic T-cell responses. Thus, it would be important to test this notion in preclinical models. Consequently, we screened the murine survivin sequence for potential binding K(b)-restricted octamer peptide epitopes. Two epitopes, which bind strongly to K(b), were selected to test their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature DC pulsed with these peptides displayed reactivity to the respective epitopes. The natural processing and presentation of these epitopes by tumor cells was evident by the killing of murine melanoma cells by vaccination-induced T cells. Subcutaneous challenge with syngeneic melanoma demonstrated the protective immunity of this vaccination. Notably, analysis of the vessel density in subcutaneous tumors revealed that survivin-specific vaccination significantly reduced the number of intratumoral vessels. In summary, we demonstrated the immunogenicity of two K(b)-restricted peptide epitopes derived from the murine survivin protein; moreover, survivin-specific vaccination not only resulted in a reduction of tumor cells but also the tumor supplying blood vessels. The presented preclinical model for survivin-directed vaccination may serve as a valuable tool to improve already running clinical trials in a syngeneic tumor model.

AB - Survivin is overexpressed in several malignancies and in tumor-associated endothelium making it an attractive target for therapeutic cytotoxic T-cell responses. Thus, it would be important to test this notion in preclinical models. Consequently, we screened the murine survivin sequence for potential binding K(b)-restricted octamer peptide epitopes. Two epitopes, which bind strongly to K(b), were selected to test their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature DC pulsed with these peptides displayed reactivity to the respective epitopes. The natural processing and presentation of these epitopes by tumor cells was evident by the killing of murine melanoma cells by vaccination-induced T cells. Subcutaneous challenge with syngeneic melanoma demonstrated the protective immunity of this vaccination. Notably, analysis of the vessel density in subcutaneous tumors revealed that survivin-specific vaccination significantly reduced the number of intratumoral vessels. In summary, we demonstrated the immunogenicity of two K(b)-restricted peptide epitopes derived from the murine survivin protein; moreover, survivin-specific vaccination not only resulted in a reduction of tumor cells but also the tumor supplying blood vessels. The presented preclinical model for survivin-directed vaccination may serve as a valuable tool to improve already running clinical trials in a syngeneic tumor model.

KW - Animals

KW - Cancer Vaccines

KW - Cell Line, Tumor

KW - Enzyme-Linked Immunosorbent Assay

KW - Epitopes, T-Lymphocyte

KW - Female

KW - H-2 Antigens

KW - Humans

KW - Immunohistochemistry

KW - Immunotherapy

KW - Inhibitor of Apoptosis Proteins

KW - Melanoma

KW - Mice

KW - Mice, Inbred C57BL

KW - Microtubule-Associated Proteins

KW - Neovascularization, Pathologic

KW - Repressor Proteins

KW - T-Lymphocytes, Cytotoxic

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/eji.200839098

DO - 10.1002/eji.200839098

M3 - Journal article

C2 - 19337999

VL - 39

SP - 1419

EP - 1424

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 5

ER -

ID: 52222421