The combination of a low-dose chemotherapeutic agent, 5-fluorouracil, and an adenoviral tumor vaccine has a synergistic benefit on survival in a tumor model system.
The combination of a low-dose chemotherapeutic agent, 5-fluorouracil, and an adenoviral tumor vaccine has a synergistic benefit on survival in a tumor model system.
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DOI：
10.1371/journal.pone.0067904
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Salem AK
中科院分区：
文献类型：
--
作者：
Geary SM;Lemke CD;Lubaroff DM;Salem AK
标准的癌症疗法，特别是那些涉及化疗的疗法，需要进行修改，以减少短期和长期副作用，并提高癌症患者的总体存活率。在这里，我们表明，结合低剂量化疗和使用腺病毒(Ad5-OVA)编码模型肿瘤相关抗原(OVA)的治疗性疫苗接种，对肿瘤挑战小鼠的存活率有协同影响。接受Ad5-OVA和小剂量5-FU联合治疗的小鼠存活率为95%，而单独接受Ad5-OVA和5-FU治疗的小鼠存活率分别为7%和30%。5-FU的存在增加了Ad5-OVA治疗小鼠脾和引流淋巴结中OVA特异性CD8+T淋巴细胞的水平，这一现象依赖于接受过肿瘤攻击的小鼠。因此，5-FU可能通过增强肿瘤特异性免疫反应和消除肿瘤体积来提高Ad5-OVA治疗小鼠的存活率。我们还调查了观察到的治疗益处可能来自5-FU耗尽MDSC群体的能力。这里提出的发现促进了腺病毒癌症疫苗与低剂量化疗相结合的概念。
Standard cancer therapies, particularly those involving chemotherapy, are in need of modifications that both reduce short-term and long-term side effects as well as improve the overall survival of cancer patients. Here we show that combining low-dose chemotherapy with a therapeutic vaccination using an adenovirus encoding a model tumor-associated antigen, ovalbumin (Ad5-OVA), had a synergistic impact on survival in tumor-challenged mice. Mice that received the combinatorial treatment of Ad5-OVA plus low-dose 5-fluorouracil (5-FU) had a 95% survival rate compared to 7% and 30% survival rates for Ad5-OVA alone and 5-FU alone respectively. The presence of 5-FU enhanced the levels of OVA-specific CD8+ T lymphocytes in the spleens and draining lymph nodes of Ad5-OVA-treated mice, a phenomenon that was dependent on the mice having been tumor-challenged. Thus 5-FU may have enhanced survival of Ad5-OVA-treated mice by enhancing the tumor-specific immune response combined with eliminating tumor bulk. We also investigated the possibility that the observed therapeutic benefit may have been derived from the capacity of 5-FU to deplete MDSC populations. The findings presented here promote the concept of combining adenoviral cancer vaccines with low-dose chemotherapy.
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影响因子：
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