Induction of Bcl-xL-specific cytotoxic T lymphocytes in mice

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

SN - 0301-6323

VL - 80

SP - 111

EP - 120

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

IS - 2

ER -