title: Immunotherapy of autologous tumor lysate-loaded dendritic cell vaccines by a closed-flow electroporation system for solid tumors.
abstract: Dendritic cell (DC)-based vaccines with the use of various antigen loading methods have been developed for cancer immunotherapy. Electroporation (EP) of a whole tumor cell lysate into DCs was previously found to be more potent for eliciting antigen-specific CD8 + T-cells compared to co-incubation of tumor cell lysates with DCs in vitro. In the present report, we studied the feasibility, safety and antitumor effect in the clinical use of an EP-DC vaccine for the immunotherapy of various types of human solid tumors. We successfully prepared an autologous tumor lysate-loaded EP-DC vaccine with high cell viability by the closed-flow electroporation system. In the phase I clinical trial, mild adverse events associated with the EP-DC vaccine were found during the treatment of advanced or recurrent cancer, or during the adjuvant therapy of some types of cancer; no autoimmune responses were observed after treatment with the autologous tumor lysate-loaded EP-DC vaccines. For the antitumor effect of the EP-DC vaccine against the 41 various types of solid tumor, the overall response rate [complete remission (CR) + partial response (PR)] was 4.9% (2/41) and the clinical benefit rate [CR+ PR + long stable disease (SD)] was 31.7% (13/41). Furthermore, the delayed-type hypersensitivity (DTH) reactivity was positive in most cases of long SD and the positive rate of DTH was 91.7% (11/12) for the patients with clinical benefit. In conclusion, the safety and feasibility of the EP-DC vaccine with autologous tumor lysates were confirmed, and it was found that the antitumor effect might be associated with the immunological response induced by the EP-DC vaccine for cancer immunotherapy.
authors.affiliation: Clinical Research Center, Seta Clinic, Tokyo, Japan. kamigaki@j-immunother.com
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamigaki
authors.forename: Toru
authors.initials: T
authors.lastname: Kaneko
authors.forename: Keiko
authors.initials: K
authors.lastname: Naitoh
authors.forename: Masashi
authors.initials: M
authors.lastname: Takahara
authors.forename: Takashige
authors.initials: T
authors.lastname: Kondo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ibe
authors.forename: Eriko
authors.initials: E
authors.lastname: Matsuda
authors.forename: Ryuji
authors.initials: R
authors.lastname: Maekawa
authors.forename: Shigenori
authors.initials: S
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018274:Electroporation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines
keywords: Electroporation; dendritic cell vaccine; solid tumor; tumor lysate