CD40-activated B cells induce anti-tumor immunity in vivo
Wennhold, Kerstin (Uniklinik Köln (Colònia, Alemanya))
Weber, Tanja M. (Uniklinik Köln (Colònia, Alemanya))
Klein-Gonzalez, Nela (Hospital Universitari Vall d'Hebron)
Thelen, Martin (Uniklinik Köln (Colònia, Alemanya))
Garcia-Marquez, Maria (Uniklinik Köln (Colònia, Alemanya))
Chakupurakal, Geothy (Uniklinik Köln (Colònia, Alemanya))
Fiedler, Anne (Uniklinik Köln (Colònia, Alemanya))
Schlösser, Hans A. (Department of General, Visceral and Cancer Surgery, University Hospital of Cologne)
Fischer, Rieke (Uniklinik Köln (Colònia, Alemanya))
Theurich, Sebastian (Max Planck Institute for Metabolism Research Cologne)
Shimabukuro-Vornhagen, Alexander (Uniklinik Köln (Colònia, Alemanya))
von Bergwelt-Baildon, Michael (Uniklinik Köln (Colònia, Alemanya))
Vall d'Hebron Institut de Recerca (VHIR)
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	The introduction of checkpoint inhibitors represents a major advance in cancer immunotherapy. Some studies on checkpoint inhibition demonstrate that combinatorial immunotherapies with secondary drivers of anti-tumor immunity provide beneficial effects for patients that do not show a strong endogenous immune response. CD40-activated B cells (CD40B cells) are potent antigen presenting cells by activating and expanding naïve and memory CD4 + and CD8 + and homing to the secondary lymphoid organs. In contrast to dendritic cells, the generation of highly pure CD40B cells is simple and time efficient and they can be expanded almost limitlessly from small blood samples of cancer patients. Here, we show that the vaccination with antigen-loaded CD40B cells induces a specific T-cell response in vivo comparable to that of dendritic cells. Moreover, we identify vaccination parameters, including injection route, cell dose and vaccination repetitions to optimize immunization and demonstrate that application of CD40B cells is safe in terms of toxicity in the recipient. We furthermore show that preventive immunization of tumor-bearing mice with tumor antigen-pulsed CD40B cells induces a protective anti-tumor immunity against B16. F10 melanomas and E. G7 lymphomas leading to reduced tumor growth. These results and our straightforward method of CD40B-cell generation underline the potential of CD40B cells for cancer immunotherapy.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cellular adjuvant ; CD40-activated B cells ; Cancer immunotherapy ; Antigen presentation ; B cell
Publicado en:	Oncotarget, Vol. 8 (february 2016) , p. 27740-27753, ISSN 1949-2553

DOI: 10.18632/oncotarget.7720
PMID: 26934557

14 p, 6.3 MB

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