Adoptive cell transfer therapy with ex vivo primed peripheral lymphocytes in combination with anti-PDL1 therapy effectively inhibits triple-negative breast cancer growth and metastasis.

Autor: Gammelgaard OL; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark. ogammelgaard@health.sdu.dk., Terp MG; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark., Kirkin AF; Cytovac A/S, 2970, Hørsholm, Denmark., Johansen S; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark., Traynor S; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark., Vever H; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark., Guldberg P; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark.; Danish Cancer Institute (DCI), Copenhagen, Denmark., Kodahl AR; Department of Oncology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Gjerstorff MF; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark.; Department of Oncology, Odense University Hospital, Odense, Denmark.; Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, Odense, Denmark., Ditzel HJ; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 5000, Odense C, Denmark. hditzel@health.sdu.dk.; Department of Oncology, Odense University Hospital, Odense, Denmark. hditzel@health.sdu.dk.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark. hditzel@health.sdu.dk.; Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, Odense, Denmark. hditzel@health.sdu.dk.
Jazyk: angličtina
Zdroj: Molecular cancer [Mol Cancer] 2024 Jan 06; Vol. 23 (1), pp. 6. Date of Electronic Publication: 2024 Jan 06.
DOI: 10.1186/s12943-023-01914-8
Abstrakt: Background: Adoptive cell transfer cancer immunotherapy holds promise for treating disseminated disease, yet generating sufficient numbers of lymphocytes with anti-cancer activity against diverse specificities remains a major challenge. We recently developed a novel procedure (ALECSAT) for selecting, expanding and maturating polyclonal lymphocytes from peripheral blood with the capacity to target malignant cells.
Methods: Immunodeficient mice were challenged with triple-negative breast cancer cell lines or patient-derived xenografts (PDX) and treated with allogeneic or autologous ALECSAT cells with and without anti-PDL1 therapy to assess the capacity of ALECSAT cells to inhibit primary tumor growth and metastasis.
Results: ALECSAT mono therapy inhibited metastasis, but did not inhibit primary tumor growth or prolong survival of tumor-bearing mice. In contrast, combined ALECSAT and anti-PDL1 therapy significantly inhibited primary tumor growth, nearly completely blocked metastasis, and prolonged survival of tumor-bearing mice.
Conclusions: Combined ALECSAT and anti-PDL1 therapy results in favorable anti-cancer responses in both cell line-derived xenograft and autologous PDX models of advanced triple-negative breast cancer.
(© 2023. The Author(s).)
Databáze: MEDLINE
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