title: Dendritic cells enhance the activity of human MUC1-stimulated mononuclear cells against breast cancer.
abstract: Dendritic cells (DCs) are among the most potent antigen-presenting cells (APCs), stimulating peripheral blood mononuclear cells (PBMCs) to generate antigen-specific cytotoxic T lymphocytes (CTLs). The objectives of this study were to determine if interleukin (IL)-4 is beneficial or detrimental for the generation of human DCs in vitro and to understand whether DCs generated in vitro in the presence or absence of IL-4 stimulate the killing of adenocarcinoma cells by CTLs in vivo. Mucin 1 (MUC1), a glycoprotein found on the surface of adenocarcinoma cells was used to load DCs. MUC1-loaded DCs generated in the absence of IL-4 were superior to their counterparts produced with IL-4 in stimulating PBMCs to kill human breast cancer MCF-7 cells in vitro. A corollary in vivo protection experiment was performed by injecting immunodeficient NOD-SCID mice with MCF-7 cellss.c.and MUC1-loaded CTLs, PBMCs, or DCs generated in the absence of IL-4, i.p. Mice that received CTLs and MUC1-loaded DCs on days 0, 2, 4, 9, 14 and 19 were completely protected against the development of MCF-7-derived tumors, while other schedules conferred lower protection. Therefore, tumor antigen-loaded DCs enhance the efficacy of adoptive CTL transfer, and should thus be considered for combinatorial immunotherapeutic regimens.
authors.affiliation: Departments of Internal Medicine and Biomedical Sciences; Texas Tech University Health Sciences Center Schools of Medicine and Pharmacy; Amarillo, TX USA ; Department of Life, Earth and Environmental Sciences; West Texas A & M University; Canyon, TX USA.
authors.forename: Zhenyao
authors.initials: Z
authors.lastname: Wang
authors.forename: Monte D
authors.initials: MD
authors.lastname: Hall
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Rewers-Felkins
authors.forename: Imelda S
authors.initials: IS
authors.lastname: Quinlin
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Wright
keywords: cytotoxic cells; dendritic cells; immunotherapy; protection