摘要
目的:进一步探讨贴壁树突状细胞群经骨髓瘤细胞裂解物体外脉冲的瘤苗的抗肿瘤效应。方法:从骨髓细胞和脾细胞中分离扩增培育出大量贴壁生长的树突状细胞群,进而研制了一种经骨髓瘤细胞裂解物体外脉冲的树突状细胞瘤苗,后进行动物整体实验探讨该类脉冲瘤苗的抗肿瘤效应。结果:该贴壁树突状细胞群的形态鉴定具异质性,但仍能刺激混合T淋巴细胞增殖反应。该脉冲瘤苗免疫预防效应的动物实验显示,树突状细胞的脉冲瘤苗免疫的动物能够产生且保持其特异抗肿瘤免疫保护效应,120d内反复多次攻击后未见皮下移植瘤形成。瘤苗免疫治疗效应的动物实验表示,树突状细胞的脉冲瘤苗主动免疫治疗的荷瘤动物能够获得长期生存期,荷瘤生长被抑制直至完全消退,其治愈率达100%(n=10),之后120d内未见肿瘤复发(n=5),且多次再攻击后也未见移植瘤形成(n=5)。经常规病理学尸解与镜检,实验动物皮下接种原位及其他器官均未发现骨髓瘤细胞存在,同时也未发现其他组织学异常。结论:这些结果说明脉冲的树突状细胞瘤苗具有高效的抗肿瘤预防效应、且可治愈荷瘤动物并获得免疫保护。进而提示该脉冲瘤苗主动免疫能够诱发或加强宿主体内免疫系统的抗肿瘤排斥功能,可完全抵御肿瘤细胞攻击或杀灭肿?
Aim: To develop adherent dendritic
cells(aDC) based cancer vaccine and further to investigate its antitumor immunopreventative
and immunotherapeutic effects.Methods: Recently by using a simple and convenient combined
procedure of fresh isolation and cytokines induced expansion culture, a larger number of
mouse bone marrow or spleen monuclear cell derived aDCs have been generated, and pulsed
in vitro with deactivated NS 1 myeloma cell line lysates,which were used for antitumor
immunopreventative and immunotherapeutic experiments in mice.Results: The aDCs have
heterogeneity in morphology during culture and can still stimulate proliferation of mixed T
lymphocytes in function. After vaccination of the pulsed aDC vaccine 3 times,normal animals
were primed to develop potent antitumor immunopreventation from alive tumor cells challenges
and preserve it for over 120 days,during which was found no subcutaneous implantation
tumorigenesis.After immunotherapy for model tumor bearing mice with the pulsed aDC vaccine
over 3 times,these mice had the greatly prelonged survival period,and the growth and
progression of the model tumor was restrained till whole tumor regression, the cure rate of
which was 100 % (10/10), and subsequently for over 120 days was observed no tumor
recurrence (5/5) and nor tumorigenesis (5/5)after rechallenges.By way of routine pathological
autopsy and microscope examination, in these treated animals implantation tumors in situ were
not found and nor metastases in other organs, and simultaneously other histopathological
changes were not observed. Conclusions: These results indicate that the pulsed aDC vaccine is
a safe and potent immunogen preparation and effectively primes host antitumor immune
responses.It have been concluded that active immunization with the vaccine can trigger in vivo
antitumor imumne rejection function of host immune system, which may completely resist
tumor challenges and kill and remove tumor cells as so to prevent from tumorigenesis and cure
of tumor bearing hosts.
出处
《河南医科大学学报》
1999年第1期40-44,共5页
Journal of Henan Medical University
基金
河南医科大学回国人员科研启动基金
河南医科大学基础医学院科研基金
河南省教委重点攻关项目
河南省科委重点攻关项目
关键词
树突状细胞
瘤苗
骨髓肿瘤
免疫疗法
小鼠
dendritic cells
cancer vaccines
myeloma
cell
culture
immunopreventation
immunotherapy
tumor bearing mice