Informace o publikaci

A replicating LCMV-based vaccine for the treatment of solid tumors

Autoři	METTE-TRIIN Purde CUPOVIC Jovana PALMOWSKI Yannick A MAKKY Ahmad SCHMIDT Sarah ROCHWARGER Alexander HARTMANN Fabienne STEMESEDER Felix LERCHER Alexander MARIE-THERESE Abdou BOMZE David BEŠŠE Lenka BERNER Fiamma TÜTING Thomas HÖLZEL Michael BERGTHALER Andreas KOCHANEK Stefan LUDEWIG Burkhard LAUTERBACH Henning ORLINGER Klaus K BALD Tobias SCHIETINGER Andrea SCHÜRCH Christian RING Sandra S FLATZ Lukas
Rok publikování	2024
Druh	Článek v odborném periodiku
Časopis / Zdroj	Molecular Therapy
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://www.sciencedirect.com/science/article/pii/S1525001623006597?via%3Dihub
Doi	http://dx.doi.org/10.1016/j.ymthe.2023.11.026
Klíčová slova	adoptive cell transfer; cancer immunotherapy; melanoma; self-antigens; viral-vector-based vaccines
Přiložené soubory	A_replicating_LCMV-based_vaccine_for_the_treatment_of_solid_tumors.pdf
Popis	Harnessing the immune system to eradicate tumors requires identification and targeting of tumor antigens, including tumor-specific neoantigens and tumor-associated self-antigens. Tumor-associated antigens are subject to existing immune tolerance, which must be overcome by immunotherapies. Despite many novel immunotherapies reaching clinical trials, inducing self-antigen-specific immune responses remains challenging. Here, we systematically investigate viral-vector-based cancer vaccines encoding a tumor-associated self-antigen (TRP2) for the treatment of established melanomas in preclinical mouse models, alone or in combination with adoptive T cell therapy. We reveal that, unlike foreign antigens, tumor-associated antigens require replication of lymphocytic choriomeningitis virus (LCMV)-based vectors to break tolerance and induce effective antigen-specific CD8+ T cell responses. Immunization with a replicating LCMV vector leads to complete tumor rejection when combined with adoptive TRP2-specific T cell transfer. Importantly, immunization with replicating vectors leads to extended antigen persistence in secondary lymphoid organs, resulting in efficient T cell priming, which renders previously “cold” tumors open to immune infiltration and reprograms the tumor microenvironment to “hot.” Our findings have important implications for the design of next-generation immunotherapies targeting solid cancers utilizing viral vectors and adoptive cell transfer.
Související projekty:	Národní ústav pro výzkum rakoviny