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乳腺癌细胞抗原负载的自体树突状细胞体内诱导特异性T细胞应答 被引量:7

Specific T-cell response induced in vivo by dendritic cells loaded with breast tumor cells antigen
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摘要 目的 以乳腺癌细胞抗原体外负载自体树突状细胞(DCs)对24例乳腺癌患者进行自身免疫,探讨其体内诱导特异性T细胞免疫应答的能力.方法 新鲜癌组织制备成热休克凋亡细胞抗原负载外周单核细胞来源DC,分别在采血后第1、2、4、6周于患者腹股沟淋巴结富集区进行皮内注射,细胞剂量为4×10^6~6×10^6/次.结果 DC免疫治疗后患者血清抗瘤免疫因子水平明显上升:白细胞介素(IL)-2治疗前为(33.8±7.2)ng/L,治疗后为(68.5±12.4)ng/L;IL-12治疗前为(48.5±10.9)ng/L,治疗后为(118.2±31.5)ng/L;肿瘤坏死因子(TNF)-α治疗前为(18.7±5.3)ng/L,治疗后为(78.3±11.5)ng/L;干扰素(IFN)-γ治疗前为(20.5±6.3)ng/L,治疗后为(92.6±14.9)ng/L,治疗前后比较差异有统计学意义(P〈0.01);DTH试验阳性率为7/10;4/10例IFN-γ+CD8+T细胞频率较治疗前明显增加.随访发现:除1例患者在治疗后3个月内疾病进展(PD),其余患者病情稳定无复发与转移症状(SD).结论 以乳腺癌细胞为抗原负载自体DC免疫患者,能够有效提高患者非特异免疫水平,激发体内特异性T细胞免疫应答,是一种安全、副反应较小、有效的乳腺癌辅助治疗手段. Objective To explore the potential of autologous dendritic cells (DCs) loaded with breast tumor cells antigen in inducing tumor-specific T cells response in vivo. Methods Fresh tumor samples from patients with breast cancer were collected and made into apoptotic heat shock tumor cells. Peripheral blood mononuclear cells (PBMCs) were isolated. DCs were induced from monocytes with granulocytemacrophage colony-stimulating factor (rhGM-CSF) and interleukin-4 (rhIL-4) combination for 5 days. DCs were co-cultured with autologous apoptotic heat shock tumor cells for 48 h. Twenty-four patients with breast cancers received four vaccinations of auto-DCs at 1 st, 2nd, 4th, and 6th week with cell number from 4×10^6 to 6×10^6. Results The vaccinations were well tolerated, and most patients experienced improved quality of life after DC immunization. Cytokine levels including IL-2, IL-12, TNF-α and IFN-γ in sera were obviously increased after DC vaccination [(68. 5±12. 4), (118. 2±31. 5), (78. 3±11.5) and (92. 6±14. 9) ng/L respectively] as compared with those before vaccinations [(33. 8±7. 2), (48. 5±10. 9), (18. 7±5. 3 ) and (20. 5±6. 3) ng/L respectively]. Both antigen specific delayed type hypersensitivity (DTH) reaction and the frequency of antigen specific IFN-gamma+CD8^+T lymphocytes were examined after 4 times of DC vaccinations. The DTH tests were positive in 7 out of 10 patients. The frequency of IFN-γ^+CD8^+T cells was enhanced in 4 out of 10 patients. One out of 24 patients experienced a progressive disease, while the others showed no progress during a follow-up period of 34 months. Conclusion Autologous DCs loaded with heat-shocked apoptotic breast cancer cells antigen elicit specific anti-tumor T cell immune responses companying with high levels of Thl type cytokine secretion. DCs vaccination after surgery may be a novel and effective combination tool for tumor treatment.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2010年第6期708-710,共3页 Chinese Journal of Experimental Surgery
基金 江苏省卫生厅社会发展科技计划项目(H200525) 常州市社会发展科技计划项目(S2007215)
关键词 乳腺癌 树突状细胞 免疫治疗 Breast carcinoma Dendritic cells Immunotherapy
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  • 1Yee C,Thompson JA,Byrd D,et al.Adoptive T cell therapy using antigenspecific+T cell clones for the treatment of patients with metastatic CD8melanoma:in vivo persistence,migration,and antitumor effect of transferred Tcells.Proc Natl Acad Sci USA,2002,99:16168-16173.
  • 2Shi HZ,Cao TH,John EC,et al.Hyperthermia enhances CTL CrossPriming.The Journal of Immunology,2006,176:2134-2141.
  • 3孟淑芳,林林,李修兰,冯建平,王佑春,李德富.软琼脂克隆法与裸鼠体内接种法检测细胞致瘤性的比较[J].中国生物制品学杂志,2006,19(5):516-519. 被引量:22
  • 4Christopher J,Wheeler AD,Keith L,et al.Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients.Cancer Res,2008,68:5955-5964.

二级参考文献6

  • 1WHO Technical Report Series,No.878,1998,Annex 1:Requirements for the used of animal cells as in vitro substrated for the production of biologicals.
  • 2Davis JM.Basic cell culture.Oxford University Press,2002.
  • 3FDA.Points to consider in the characterization of cell lines used to produce biologicals.1993.
  • 4Hirose K,Hakozaki N,Nyunova Y,et al.Chemokine gene transfection into tumout cells reduced tumorigenicity in nude mice in association with neurtrophilic infiltration.Br J Cancer,1995,72 (3):708-714.
  • 5Vincent-Falquet JC,Peyron L,Souvras M,et al.Qualification of working cell banks for the vero cell line to produce licensed human vaccines.Developments in Biological Standardization,1989,70:153-156.
  • 6Petricciani JC,Levenbook IS,Wierenga DE,et al.Early passage primate cell immotality is independent of tumorigenicity.In Vitro Cell Dev Biol,1987,23(7):523-526.

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  • 1董广为,杜智敏,杨宝峰.大鼠结肠癌淋巴转移时树突状细胞的表达[J].哈尔滨医科大学学报,2005,39(3):224-225. 被引量:1
  • 2佟盼琢,张祥宏,严霞,王俊灵,张国建.杂色曲霉素对人食管鳞状上皮细胞人类白细胞抗原Ⅰ分子表达的影响[J].中华实验外科杂志,2006,23(4):583-584. 被引量:5
  • 3黎剑,詹文华,蔡世荣,Bembenek,A,Schlag,PM.乳腺癌淋巴结微小转移状态下前哨与非前哨淋巴结免疫细胞的改变[J].中华实验外科杂志,2007,24(1):7-8. 被引量:4
  • 4曾而明,袁贤瑞,李东海,洪涛,邹安琪,李美华,徐庚生.人类白细胞抗原-G蛋白在星形细胞肿瘤组织的表达[J].中华实验外科杂志,2007,24(1):118-118. 被引量:3
  • 5Czerniecki BJ,Koski GK,Koldovsky U,et al.Targeting HER-2/neu in early breast cacer development using dendritic cells withstaged interleukin-12 burst secretion[J].Cancer Res,2007,67(4):1842-1852.
  • 6Spector NL,Blackwell KL.Understanding the mechanisms behindtrastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer[J].J Clin Oncol,2009,27(34):5838-5847.
  • 7Yee C,Thompson JA,Byrd D,et al.Adoptive T cell therapyusing antigen-specific+T cell clones for the treatment of patientswith metastatic CD8 melanoma:In vivo persistence,migration,and antitumor effect of transferred T cells[J].Proc Natl Acad SciU S A,2002,99(25):16168-16173.
  • 8Draube A,Klein-Gonzalez N,Mattheus S,et al.Dendritic cellbased tumor vaccination in prostate and renal cell cancer:A sys-tematic review and meta-analysis[J].PLoS One,2011,6(4):1-11.
  • 9Celestia SH,Paul FS,Eric JS,et al.Integrated data from 2 ran-domized,double-blind,placebo-controlled,phase 3 trials of activecellular immunotherapy with Sipuleucel-T in advanced prostatecancer[J].Cancer,2009,115(15):3670-3679.
  • 10May KF Jr,Gulley JL,Drake CG,et al.Prostate cancer immuno-therapy[J].Clin Cancer Res,2011,17(16):5233-5238.

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