Immunogenicity of constitutively active V599EBRaf

Mads Hald Andersen; Joachim Fensterle; Selma Ugurel; Sine Reker Hadrup; Roland Houben; Per Guldberg; Thomas G. Berger; Dirk Schadendorf; Uwe Trefzer; Eva B. Bröcker; Per Thor Straten; Ulf R. Rapp; Jürgen C. Becker

doi:10.1158/0008-5472.can-04-0937

Immunogenicity of constitutively active V599EBRaf

Mads Hald Andersen
, Joachim Fensterle
, Selma Ugurel
, Sine Reker Hadrup
, Roland Houben
, Per Guldberg
, Thomas G. Berger
, Dirk Schadendorf
, Uwe Trefzer
, Eva B. Bröcker
, Per Thor Straten
, Ulf R. Rapp
, Jürgen C. Becker

Danish Cancer Society
University of Würzburg
German Cancer Research Center
Universitätsklinikum Erlangen
Charité – Universitätsmedizin Berlin

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Activating BRAF somatic missense mutations within the kinase domain are present in 60-66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.

Original language	English
Journal	Cancer Research
Volume	64
Issue number	15
Pages (from-to)	5456-5460
Number of pages	5
ISSN	0008-5472
DOIs	https://doi.org/10.1158/0008-5472.can-04-0937
Publication status	Published - 2004
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cancer Research
Oncology
B Raf kinase
epitope
gene product
glutamic acid
HLA B antigen
mutant protein
unclassified drug
valine
amino acid substitution
antigen recognition
article
braf gene
cell clone
cell selection
cellular immunity
clonal selection
controlled study
cytotoxic T lymphocyte
gene
genotype
host
human
human cell
immunogenicity
immunoselection
major histocompatibility complex restriction
melanoma
melanoma cell
metastasis
missense mutation
priority journal
somatic mutation
tumor bearing host
tumor growth
wild type
Disease Progression
Epitopes
Genotype
HLA-B Antigens
Humans
Melanoma
Mutation, Missense
Peptide Fragments
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-raf
Skin Neoplasms
T-Lymphocytes, Cytotoxic

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10.1158/0008-5472.can-04-0937

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title = "Immunogenicity of constitutively active V599EBRaf",

abstract = "Activating BRAF somatic missense mutations within the kinase domain are present in 60-66\% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.",

keywords = "Cancer Research, Oncology, B Raf kinase, epitope, gene product, glutamic acid, HLA B antigen, mutant protein, unclassified drug, valine, amino acid substitution, antigen recognition, article, braf gene, cell clone, cell selection, cellular immunity, clonal selection, controlled study, cytotoxic T lymphocyte, gene, genotype, host, human, human cell, immunogenicity, immunoselection, major histocompatibility complex restriction, melanoma, melanoma cell, metastasis, missense mutation, priority journal, somatic mutation, tumor bearing host, tumor growth, wild type, Disease Progression, Epitopes, Genotype, HLA-B Antigens, Humans, Melanoma, Mutation, Missense, Peptide Fragments, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins c-raf, Skin Neoplasms, T-Lymphocytes, Cytotoxic",

author = "Andersen, \{Mads Hald\} and Joachim Fensterle and Selma Ugurel and Hadrup, \{Sine Reker\} and Roland Houben and Per Guldberg and Berger, \{Thomas G.\} and Dirk Schadendorf and Uwe Trefzer and Br{\"o}cker, \{Eva B.\} and Straten, \{Per Thor\} and Rapp, \{Ulf R.\} and Becker, \{J{\"u}rgen C.\}",

year = "2004",

doi = "10.1158/0008-5472.can-04-0937",

language = "English",

volume = "64",

pages = "5456--5460",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research",

number = "15",

}

TY - JOUR

T1 - Immunogenicity of constitutively active V599EBRaf

AU - Andersen, Mads Hald

AU - Fensterle, Joachim

AU - Ugurel, Selma

AU - Hadrup, Sine Reker

AU - Houben, Roland

AU - Guldberg, Per

AU - Berger, Thomas G.

AU - Schadendorf, Dirk

AU - Trefzer, Uwe

AU - Bröcker, Eva B.

AU - Straten, Per Thor

AU - Rapp, Ulf R.

AU - Becker, Jürgen C.

PY - 2004

Y1 - 2004

N2 - Activating BRAF somatic missense mutations within the kinase domain are present in 60-66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.

AB - Activating BRAF somatic missense mutations within the kinase domain are present in 60-66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.

KW - Cancer Research

KW - Oncology

KW - B Raf kinase

KW - epitope

KW - gene product

KW - glutamic acid

KW - HLA B antigen

KW - mutant protein

KW - unclassified drug

KW - valine

KW - amino acid substitution

KW - antigen recognition

KW - article

KW - braf gene

KW - cell clone

KW - cell selection

KW - cellular immunity

KW - clonal selection

KW - controlled study

KW - cytotoxic T lymphocyte

KW - gene

KW - genotype

KW - host

KW - human

KW - human cell

KW - immunogenicity

KW - immunoselection

KW - major histocompatibility complex restriction

KW - melanoma

KW - melanoma cell

KW - metastasis

KW - missense mutation

KW - priority journal

KW - somatic mutation

KW - tumor bearing host

KW - tumor growth

KW - wild type

KW - Disease Progression

KW - Epitopes

KW - Genotype

KW - HLA-B Antigens

KW - Humans

KW - Melanoma

KW - Mutation, Missense

KW - Peptide Fragments

KW - Proto-Oncogene Proteins B-raf

KW - Proto-Oncogene Proteins c-raf

KW - Skin Neoplasms

KW - T-Lymphocytes, Cytotoxic

U2 - 10.1158/0008-5472.can-04-0937

DO - 10.1158/0008-5472.can-04-0937

M3 - Journal article

SN - 0008-5472

VL - 64

SP - 5456

EP - 5460

JO - Cancer Research

JF - Cancer Research

IS - 15

ER -

Immunogenicity of constitutively active V599EBRaf

Abstract

UN SDGs

Keywords

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