An effective vaccine against colon cancer in mice: use of recombinant adenovirus interleukin-12 transduced dendritic cells.

An effective vaccine against colon cancer in mice: use of recombinant adenovirus interleukin-12 transduced dendritic cells.
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一种有效的小鼠结肠癌疫苗:使用重组腺病毒白介素 12 转导的树突状细胞。

DOI:
10.3748/wjg.14.532
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发表时间:
2008
影响因子:
4.3
通讯作者:
Yan
Yan
中科院分区:
医学2区
文献类型:
--
作者:
Xiao;Liang Wang;Yan

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目的 目的探讨重组腺病毒白细胞介素12(AdVIL-12)转导的树突状细胞(DCs)疫苗对小鼠结肠癌的治疗作用。 方法 DC和AdVIL-12以不同的时间间隔和不同的剂量一起孵育。收集上清液并通过酶联免疫吸附测定(ELISA)测试IL-12。为了确定肿瘤细胞裂解物脉冲的(TP)AdVIL-12/DC是否增强所建立的肿瘤模型中的治疗潜力,将CT 26结肠肿瘤细胞皮下(s.c.)在幼稚BALB/c小鼠的中胁腹中。在第3天和第10天,用CT 26 TP AdVIL-12/DC的疫苗接种荷瘤小鼠。作为保护性结肠肿瘤模型,将幼稚BALB/c小鼠皮下免疫。用CT 26 TP AdVIL-12/DC以7天的间隔两次在他们的小鼠中接种。第7天免疫后,用致死剂量的CT 26肿瘤细胞攻击小鼠,并评估存活时间。随后,在免疫小鼠中评价细胞毒性T淋巴细胞(CTL)活性和干扰素γ(IFN γ)分泌,并离体测定CTL。 结果 小鼠DCs经逆转录病毒转导后,分泌高水平的IL-12(AdVIL-12/DCs,615.27+/-42.3pg/mL vs DCs,46.32+/-7.29pg/mL,P<0.05)。接种CT 26 TP AdVIL-12/DCs可以增强小鼠治疗模型(第19天肿瘤体积:CT 26 TP AdVIL-12/DCs 107+/-42 mm 3 vs CT 26 TP DCs 383+/-65 mm 3,P<0.05)和保护模型中针对CT 26结肠肿瘤的抗肿瘤免疫力。此外,CT 26 TP AdVIL-12/DC疫苗接种增强了肿瘤特异性CTL活性,在免疫小鼠中产生高水平的IFN γ。体外用AdVIL-12/DC致敏的T细胞比用CT 26 TP/DC致敏的T细胞能够诱导更有效的CTL活性(E:T=100:1,69.49%+/-6.11%特异性裂解vs 37.44%+/-4.32%特异性裂解,P<0.05)。 结论 用重组AdVIL-12转导的DC脉冲的肿瘤细胞裂解物接种增强小鼠对结肠癌的特异性抗肿瘤免疫。
AIM To investigate the effect of a vaccine with recombinant adenovirus interleukin-12 (AdVIL-12) transduced dendritic cells (DCs) against colon cancer in mice. METHODS DCs and AdVIL-12 were incubated together at different time intervals and at different doses. Supernatant was collected and tested for IL-12 by enzyme-linked immunosorbent assay (ELISA). In order to determine whether tumor cell lysate-pulsed (TP) AdVIL-12/DCs enhance therapeutic potential in the established tumor model, CT26 colon tumor cells were implanted subcutaneously (s.c.) in the midflank of naive BALB/c mice. Tumor-bearing mice were injected with a vaccination of CT26 TP AdVIL-12/DCs on d 3 and 10. As a protective colon tumor model, naive BALB/c mice were immunized s.c. in their abdomens with CT26 TP AdVIL-12/DCs twice at seven day intervals. After the immunization on d 7, the mice were challenged with a lethal dose of CT26 tumor cells and survival times were evaluated. Subsequently, cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFNgamma) secretion was evaluated in the immunized mice, and assayed CTL ex vivo. RESULTS Murine DCs were retrovirally transduced with AdVIL-12 efficiency, and the AdVIL-12 transduced DCs secreted a high level of IL-12 (AdVIL-12/DCs, 615.27+/-42.3 pg/mL vs DCs, 46.32+/-7.29 pg/mL, P<0.05). Vaccination with CT26 TP AdVIL-12/DCs could enhance anti-tumor immunity against CT26 colon tumor in murine therapeutic models (tumor volume on d 19: CT26 TP AdVIL-12/DCs 107+/-42 mm3 vs CT26 TP DCs 383+/-65 mm3, P<0.05) and protective models. Moreover, the CT26 TP AdVIL-12/DC vaccination enhances tumor-specific CTL activity, producing high levels of IFNgamma in immunized mice. Ex vivo primed T cells with AdVIL-12/DCs were able to induce more effective CTL activity than in primed T cells with CT26 TP/DCs (E:T=100:1, 69.49%+/-6.11% specific lysis vs 37.44%+/-4.32% specific lysis, P<0.05). CONCLUSION Vaccination with recombinant AdVIL-12 transduced DC pulsed tumor cell lysate enhance anti-tumor immunity specific to colon cancer in mice.
DOI: --
发表时间: 2006-10
影响因子: --
作者:
D. Stone;A. Lieber
通讯作者: D. Stone;A. Lieber
DOI: 10.4049/jimmunol.161.2.927
发表时间: 1998-07
影响因子: 4.4
作者:
C. Tannenbaum;R. Tubbs;D. Armstrong;J. Finke;R. Bukowski;T. Hamilton
通讯作者: C. Tannenbaum;R. Tubbs;D. Armstrong;J. Finke;R. Bukowski;T. Hamilton
DOI: 10.1172/jci10128
发表时间: 2001-07
期刊: The Journal of clinical investigation
影响因子: --
作者:
J. Wigginton;E. Gruys;L. Geiselhart;J. Subleski;K. Komschlies;J. Park;T. Wiltrout;K. Nagashima
通讯作者: J. Wigginton;E. Gruys;L. Geiselhart;J. Subleski;K. Komschlies;J. Park;T. Wiltrout;K. Nagashima
人类树突状细胞经过基因工程改造,可表达高水平的人类上皮肿瘤抗原粘蛋白 (MUC-1)。
DOI: --
发表时间: 1996
期刊: Cancer research.
影响因子: --
作者:
Henderson,RA;Nimgaonkar,MT;Watkins,SC;Robbins,PD;Ball,ED;Finn,OJ
通讯作者: Finn,OJ