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含 WKYMVm 的联合制剂在异位肿瘤动物模型中引发强烈的抗肿瘤活性。

A WKYMVm-containing combination elicits potent anti-tumor activity in heterotopic cancer animal model.

机构信息

Department of Biological Sciences, Sungkyunkwan University, Suwon, South Korea.

出版信息

PLoS One. 2012;7(1):e30522. doi: 10.1371/journal.pone.0030522. Epub 2012 Jan 25.

DOI:10.1371/journal.pone.0030522
PMID:22295090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3266298/
Abstract

The development of efficient anti-cancer therapy has been a topic of intense interest for several decades. Combined administration of certain molecules and immune cells has been shown to be an effective form of anti-cancer therapy. Here, we examined the effects of administering an immune stimulating peptide (WKYMVm), 5-fluoro-uracil (5-FU), and mature dendritic cells (mDCs) against heterotopic cancer animal model. Administration of the triple combination strongly reduced tumor volume in CT-26-inoculated heterotopic cancer animal model. The induced anti-tumor activity was well correlated with FAS expression, caspase-3 activation, and cancer cell apoptosis. The triple combination treatment caused recruitment of CD8 T lymphocytes and natural killer (NK) cells into the tumor. The production of two cytokines, IFN-γ and IL-12, were strongly stimulated by administration of the triple combination. Depletion of CD8 T lymphocytes or NK cells by administration of anti-CD8 or anti-asialoGM1 antibody inhibited the anti-tumor activity and cytokine production of the triple combination. The triple combination strongly inhibited metastasis of colon cancer cells in a heterotopic cancer animal model as well as in a metastatic cancer animal model, and enhanced the survival rate of the mice model. Adoptive transfer of CD8 T lymphocytes and NK cells further increased the survival rate. Taken together, we suggest that the use of triple combination therapy of WKYMVm, 5-FU, and mDCs may have implications in solid tumor and metastasis treatment.

摘要

几十年来，开发有效的抗癌疗法一直是人们关注的焦点。联合使用某些分子和免疫细胞已被证明是一种有效的抗癌疗法。在这里，我们研究了给予免疫刺激肽（WKYMVm）、5-氟尿嘧啶（5-FU）和成熟树突状细胞（mDCs）对异位癌动物模型的影响。三重联合给药强烈降低了 CT-26 接种异位癌动物模型中的肿瘤体积。诱导的抗肿瘤活性与 FAS 表达、半胱天冬酶-3 激活和癌细胞凋亡密切相关。三重联合治疗导致 CD8 T 淋巴细胞和自然杀伤（NK）细胞招募到肿瘤中。三重联合给药强烈刺激两种细胞因子 IFN-γ和 IL-12 的产生。通过给予抗 CD8 或抗 asialoGM1 抗体耗尽 CD8 T 淋巴细胞或 NK 细胞，抑制了三重联合的抗肿瘤活性和细胞因子产生。三重联合强烈抑制了异位癌动物模型和转移癌动物模型中结肠癌细胞的转移，并提高了小鼠模型的存活率。CD8 T 淋巴细胞和 NK 细胞的过继转移进一步提高了存活率。综上所述，我们认为 WKYMVm、5-FU 和 mDCs 的三重联合治疗可能对实体瘤和转移治疗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/3e7563f3b2e7/pone.0030522.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/174909f1a974/pone.0030522.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/73f8d80668a9/pone.0030522.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/8c1e56e6c9b5/pone.0030522.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/3e7563f3b2e7/pone.0030522.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/174909f1a974/pone.0030522.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/44231408eb9c/pone.0030522.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/fb50b8b67ccf/pone.0030522.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/8d910937c7a5/pone.0030522.g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/8c1e56e6c9b5/pone.0030522.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f76/3266298/3e7563f3b2e7/pone.0030522.g007.jpg

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