Li Yang, Huang Shao-Liang, Zhang Xu-Chao, Fang Jian-Pei, Wu Yan-Feng, Wei Jing, Huang Wen-Ge, Zhou Dun-Hua, Huang Ke, Lin Yong-Chao
Pediatric Department, Second Affiliated Hospital, SUN Yat-sen University, Guangzhou 510120, China.
Zhonghua Xue Ye Xue Za Zhi. 2008 Jan;29(1):39-43.
To study the in vivo efficacy and the safety of cord blood derived CIK/NK cells stimulated by K562-dendritic cells (DC) fusion vaccines in NOD/SCID mice model for human erythroleukemia.
DC and CIK /NK cells were both derived from cord blood mononuclear cells. DC were fused with inactivated K562 leukemia cell by PEG to produce K562-DC fusion vaccines. K562-DC fusion vaccines were co-cultured with CIK/NK cells to prepare K562-DC fusion vaccine stimulated CIK/NK cells. NOD/SCID mice were inoculated with 1 x 10(6) K562 cells. 24 hours later, 1 x 10(7) vaccines stimulated CIK/ NK cells and 1 x 10(7) CIK/NK cells were transfused into the NOD/SCID mice. NOD/SCID mice without inoculation of K562 cells were used as control group. CD13 and CD56 positive cells were assayed by flow cytometry.
All the leukemia NOD/SCID mice without therapy died within 39 days, tumor was found in 5 of 8 mice. One of 8 leukemia mice treated with K562-DC fusion vaccines stimulated CIK/NK cells died at the 65th day, the anti-tumor response rate was 87.5%. Two of the leukemia mice treated with CIK/NK cells died at the 56th and 65th day respectively, the anti-tumor response rate was 75%. There was no significant difference in survival time between these two groups, and both survivals were longer than that of the control group. There was no significant difference in CD13 positive cells in the survival mice between these two groups, and both of that were less than that of the control mice. There was no significant difference in CD56 positive cells between the two treated groups and the control group.
Cord blood derived CIK/ NK cells stimulated by inactivated tumor cells retain the cytotoxicity and do not develop tumor in vivo.
在人红白血病的NOD/SCID小鼠模型中研究K562 - 树突状细胞(DC)融合疫苗刺激的脐血来源CIK/NK细胞的体内疗效和安全性。
DC和CIK/NK细胞均来源于脐血单个核细胞。DC与灭活的K562白血病细胞通过聚乙二醇融合以产生K562 - DC融合疫苗。K562 - DC融合疫苗与CIK/NK细胞共培养以制备K562 - DC融合疫苗刺激的CIK/NK细胞。给NOD/SCID小鼠接种1×10(6)个K562细胞。24小时后,将1×10(7)个疫苗刺激的CIK/NK细胞和1×10(7)个CIK/NK细胞输注到NOD/SCID小鼠体内。未接种K562细胞的NOD/SCID小鼠作为对照组。通过流式细胞术检测CD13和CD56阳性细胞。
所有未经治疗的白血病NOD/SCID小鼠在39天内死亡,8只小鼠中有5只发现肿瘤。用K562 - DC融合疫苗刺激的CIK/NK细胞治疗的8只白血病小鼠中有1只在第65天死亡,抗肿瘤反应率为87.5%。用CIK/NK细胞治疗的2只白血病小鼠分别在第56天和第65天死亡,抗肿瘤反应率为75%。这两组的生存时间无显著差异,且两者的生存期均长于对照组。这两组存活小鼠的CD13阳性细胞无显著差异,且两者均低于对照小鼠。两个治疗组与对照组之间的CD56阳性细胞无显著差异。
灭活肿瘤细胞刺激的脐血来源CIK/NK细胞保留细胞毒性且在体内不会形成肿瘤。