title: Preparation of fully activated dendritic cells capable of priming tumor-specific cytotoxic T lymphocytes in patients with metastatic cancer using penicillin-killed streptococcus pyogenes (OK432) and anti-CD40 antibody.
abstract: In order to achieve sufficient therapeutic potency, it has been proposed that vaccine therapy with dendritic cells needs to be combined with manipulation of immunological checkpoints, such as inhibition of regulatory T cells and blockade of negative signals, and enhancement of T cell trafficking to tumor sites. In the combinatorial cancer immunotherapy, use of matured/activated dendritic cells (DCs) with more potent antigen presenting capacity seems to be essential for eliciting anti-tumor immune responses. We herein established an ex vivo induction strategy for activated DCs capable of eliciting efficient tumor antigen-specific cytotoxic T lymphocytes (CTLs) from patients with metastatic cancer as well as healthy donors. Immature DCs were matured by 48-h culture in the presence of anti-CD40 antibody and penicillin-killed streptococcus pyogenes (OK432). Supplementation with both anti-CD40 and OK432 resulted in induction of activated DCs with higher surface expression of CD80, CD83, CD86 and major histocompatibility complex class II antigens, compared with other mature DCs that were induced by the combination of anti-CD40 with tumor necrosis factor-alpha or lipopolysaccharide. In analysis of the produced cytokine profiles, the activated DCs produced the highest T-helper 1-type cytokines for at least 72 h. Furthermore, the activated DCs, pulsed with tumor-associated antigen peptide, elicited in vitro tumor-specific CTLs, but DCs activated with other combinations did not in cancer patients. Therefore, we suggest that the activated DCs studied here might be used as a basic element for the combinatorial cancer immunotherapy.
authors.affiliation: Second Department of Surgery, Kagawa University, Faculty of Medicine, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kontani
authors.forename: Koji
authors.initials: K
authors.lastname: Teramoto
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Sawai
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tezuka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ishida
authors.forename: Kiichi
authors.initials: K
authors.lastname: Kajino
authors.forename: Shozo
authors.initials: S
authors.lastname: Fujino
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
authors.forename: Reiji
authors.initials: R
authors.lastname: Kannagi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yokomise
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ogasawara
mesh_terms: D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D015703:Antigens, CD / Q000032:analysis; D019013:CD40 Antigens / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010406:Penicillins / Q000494:pharmacology; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D019013:CD40 Antigens; D016207:Cytokines; D010406:Penicillins; D007371:Interferon-gamma