Augmenting therapy of ovarian cancer efficacy by secreting IL-21 human umbilical cord blood stem cells in nude mice.
In the present study, CD34(+) human umbilical cord blood stem cells (UCBSCs) were engineered to express interleukin-21 (IL-21) and then were transplanted into A2780 ovarian cancer xenograft-bearing Balb/c nude mice. The therapeutic efficacy of this procedure on ovarian cancer was evaluated. The findings from the study indicated that UCBSCs did not form gross or histological teratomas until up to 70 days postinjection. The CD34(+) UCBSC-IL-21 therapy showed a consistent effect in the ovarian cancer of the treated mice, delaying the tumor appearance, reducing the tumor sizes, and extending life expectancy. The efficacy was attributable to keeping CD34(+) UCBSC-IL-21 in the neoplastic tissues for more than 21 days. The secreted IL-21 not only increased the quantity of CD11a(+) and CD56(+) NK cells but also increased NK cell cytotoxicities to YAC-1 cells and A2780 cells, respectively. The efficacy was also associated with enhancing the levels of IFN-γ, IL-4, and TNF-α in the mice as well as the high expressions of the NKG2D and MIC A/B molecules in the tumor tissues. This study suggested that transferring CD34(+) UCBSC-IL-21 into the nude mice was safe and feasible in ovarian cancer therapy, and that the method would be a promising new strategy for clinical treatment of ovarian cancer.
Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Nanjing, China.
Weihua
W
Hu
Jing
J
Wang
Jun
J
Dou
Xiangfeng
X
He
Fengshu
F
Zhao
Cuilian
C
Jiang
Fangliu
F
Yu
Kai
K
Hu
Lili
L
Chu
Xiaoli
X
Li
Ning
N
Gu
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098546:Interleukin-21
D018952:Antigens, CD34; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D007378:Interleukins; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D000098546:Interleukin-21