Immunotherapy of autologous tumor lysate-loaded dendritic cell vaccines by a closed-flow electroporation system for solid tumors

摘要

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.