Cytokine-Based Log-Scale Expansion of Functional Murine Dendritic Cells |
| |
| Authors: | Yui Harada Yasuji Ueda Hiroaki Kinoh Atsushi Komaru Terumi Fuji-Ogawa Aki Furuya Akihiro Iida Mamoru Hasegawa Tomohiko Ichikawa Yoshikazu Yonemitsu |
| |
| Affiliation: | 1. Department of Gene Therapy, Chiba University Graduate School of Medicine, Chiba, Japan.; 2. Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.; 3. DNAVEC Corporation, Tsukuba, Ibaraki, Japan.; 4. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.;New York University School of Medicine, United States of America |
| |
| Abstract: | BackgroundLimitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies.Methodology/Principal FindingsFloating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines.Conclusions/SignificanceThe concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy. |
| |
| Keywords: | |
|
|
