title: Impaired tumor antigen processing by immunoproteasome-expressing CD40-activated B cells and dendritic cells.
abstract: Professional APCs, such as dendritic cells, are routinely used in vitro for the generation of cytotoxic T lymphocytes specific for tumor antigens. In addition to dendritic cells, CD40-activated B cells and variant K562 leukemic cells can be readily transfected with nucleic acids for in vitro and in vivo antigen presentation. However, the expression of immunoproteasome components in dendritic cells may preclude display of tumor antigens such as Mart1/MelanA. Here, we use three target epitopes, two derived from tumor antigens [Mart1(26-34) (M26) and Cyp1B1(239-247) (Cyp239)] and one derived from the influenza A viral antigen [FluM1(58-66) (FluM58)], to demonstrate that CD40-activated B cells, like dendritic cells, have a limited capability to process certain tumor antigens. In contrast, the K562 HLA-A*0201 transfectant efficiently processes and presents M26 and Cyp239 as well as the influenza FluM58 epitopes to T cells. These results demonstrate that the choice of target APC for gene transfer of tumor antigens may be limited by the relative efficacy of proteasome components to process certain tumor epitopes. Importantly, K562 can be exploited as an artificial APC, efficient in processing both M26 and Cyp239 epitopes and presumably, by extension, other relevant tumor antigens.
authors.affiliation: Cancer Vaccine Center, Dana-Farber Cancer Institute, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA. kanderson@partners.org
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Wanyong
authors.initials: W
authors.lastname: Zeng
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.forename: Jaewon
authors.initials: J
authors.lastname: Choi
authors.forename: Angelika B
authors.initials: AB
authors.lastname: Riemer
authors.forename: Mei
authors.initials: M
authors.lastname: Su
authors.forename: Donna
authors.initials: D
authors.lastname: Drakoulakos
authors.forename: Yoon-Joong
authors.initials: YJ
authors.lastname: Kang
authors.forename: Vladimir
authors.initials: V
authors.lastname: Brusic
authors.forename: Catherine
authors.initials: C
authors.lastname: Wu
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen