title: Simple and efficient generation of virus-specific T cells for adoptive therapy using anti-4-1BB antibody.
abstract: Although recent studies of virus-specific T-cell (VST) therapy for viral infections after allogeneic hematopoietic stem cell transplantation have shown promising results, simple and less time-intensive and labor-intensive methods are required to generate VSTs for the wider application of VST therapy. We investigated the efficacy of anti-CD28 and anti-4-1BB antibodies, which can provide T cells with costimulatory signals similar in strength to those of antigen-presenting cells, in generating VSTs. When peripheral blood mononuclear cells were stimulated with viral peptides together with isotype control, anti-CD28, or anti-4-1BB antibodies, anti-4-1BB antibodies yielded the highest numbers of VSTs, which were on an average 7.9 times higher than those generated with isotype control antibody. The combination of anti-CD28 and anti-4-1BB antibodies did not result in increased numbers of VSTs compared with anti-4-1BB antibody alone. Importantly, the positive effect of anti-4-1BB antibody was observed regardless of the epitopes of the VSTs. In contrast, the capacity of dendritic cells (DCs) to generate VSTs differed considerably depending on the epitopes of the VSTs. Furthermore, the numbers of VSTs generated with DCs were at most similar to those generated with the anti-4-1BB antibody. Generation of VSTs with anti-4-1BB antibody did not result in excessive differentiation or deteriorated function of the generated VSTs compared with those generated with control antibody or DCs. In conclusion, VSTs can be generated rapidly and efficiently by simply stimulating peripheral blood mononuclear cells with viral peptide and anti-4-1BB antibody without using antigen-presenting cells. We propose using anti-4-1BB antibody as a novel strategy to generate VSTs for adoptive therapy.
authors: *Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya †Japan Society for the Promotion of Science (JSPS), Japan.
authors: Nobuhiko
authors: N
authors: Imahashi
authors: Tetsuya
authors: T
authors: Nishida
authors: Tatsunori
authors: T
authors: Goto
authors: Seitaro
authors: S
authors: Terakura
authors: Keisuke
authors: K
authors: Watanabe
authors: Ryo
authors: R
authors: Hanajiri
authors: Reona
authors: R
authors: Sakemura
authors: Misa
authors: M
authors: Imai
authors: Hitoshi
authors: H
authors: Kiyoi
authors: Tomoki
authors: T
authors: Naoe
authors: Makoto
authors: M
authors: Murata
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D018106:CD28 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9