Induction of Bcl-xL-specific cytotoxic T lymphocytes in mice
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Induction of Bcl-xL-specific cytotoxic T lymphocytes in mice. / Larsen, Helle Kiellberg; Andersen, M H; Wandall, H H; Mathiesen, Caroline Benedicte K; Christensen, R E; Petersen, T R; Pedersen, A E.
In: Scandinavian Journal of Immunology, Vol. 80, No. 2, 08.2014, p. 111-120.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Induction of Bcl-xL-specific cytotoxic T lymphocytes in mice
AU - Larsen, Helle Kiellberg
AU - Andersen, M H
AU - Wandall, H H
AU - Mathiesen, Caroline Benedicte K
AU - Christensen, R E
AU - Petersen, T R
AU - Pedersen, A E
N1 - © 2014 John Wiley & Sons Ltd.
PY - 2014/8
Y1 - 2014/8
N2 - The induction of active immunity against tumour-associated antigens to prevent relapse of cancer is a promising approach but has so far shown only low efficacy. This low efficacy may in part be due to clonal escape of tumour cell variants by the downregulation of antigen expression or inflammation-induced dedifferentiation. Identification of novel tumour-associated antigens that at the same time are essential for continued tumour cell survival is thus critical for the development of active cancer vaccinations. At the same time, identification of novel endogenous murine tumour antigens will help improve preclinical development of cancer immunotherapy. The anti-apoptotic protein Bcl-xL has been suggested to be such an essential tumour antigen, but the lack of well-defined murine epitopes have delayed preclinical studies of Bcl-xL-targeting cancer vaccines. Here, we report the identification of two novel murine tumour-associated epitopes TAYQSFEQV and AFFSFGGAL derived from mouse Bcl-xL. Dendritic cell (DC)-based vaccination induced CD8(+) T cells capable of producing IFN-γ upon restimulation with these epitopes. Thus, our data may benefit the design of future immunotherapy strategies by providing a preclinical model for cancer vaccination with an endogenous tumour antigen that can be combined with other cancer treatments.
AB - The induction of active immunity against tumour-associated antigens to prevent relapse of cancer is a promising approach but has so far shown only low efficacy. This low efficacy may in part be due to clonal escape of tumour cell variants by the downregulation of antigen expression or inflammation-induced dedifferentiation. Identification of novel tumour-associated antigens that at the same time are essential for continued tumour cell survival is thus critical for the development of active cancer vaccinations. At the same time, identification of novel endogenous murine tumour antigens will help improve preclinical development of cancer immunotherapy. The anti-apoptotic protein Bcl-xL has been suggested to be such an essential tumour antigen, but the lack of well-defined murine epitopes have delayed preclinical studies of Bcl-xL-targeting cancer vaccines. Here, we report the identification of two novel murine tumour-associated epitopes TAYQSFEQV and AFFSFGGAL derived from mouse Bcl-xL. Dendritic cell (DC)-based vaccination induced CD8(+) T cells capable of producing IFN-γ upon restimulation with these epitopes. Thus, our data may benefit the design of future immunotherapy strategies by providing a preclinical model for cancer vaccination with an endogenous tumour antigen that can be combined with other cancer treatments.
KW - Amino Acid Sequence
KW - Animals
KW - Antigens, Neoplasm
KW - Bone Marrow Cells
KW - Cancer Vaccines
KW - Cell Line
KW - Cell Proliferation
KW - Dendritic Cells
KW - Epitopes
KW - Female
KW - Immunotherapy
KW - Interferon-gamma
KW - Mice
KW - Mice, Inbred C57BL
KW - Neoplasms
KW - T-Lymphocytes, Cytotoxic
KW - bcl-X Protein
U2 - 10.1111/sji.12192
DO - 10.1111/sji.12192
M3 - Journal article
C2 - 24846184
VL - 80
SP - 111
EP - 120
JO - Scandinavian Journal of Immunology, Supplement
JF - Scandinavian Journal of Immunology, Supplement
SN - 0301-6323
IS - 2
ER -
ID: 125182789