抑制小鼠结直肠癌模型肿瘤生长的多表位疫苗的设计和体内评价

IF 3.9 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Alisa Khodadadi, Saeid Afshar, Rezvan Najafi, Alireza Zamani, Razieh Dalirfardouei, Meysam Soleimani
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引用次数: 0

摘要

通过癌症疫苗利用免疫系统为克服肿瘤异质性提供了一个有希望的策略,这仍然是实现结直肠癌(CRC)有效治疗的最重大挑战之一。在这项研究中,我们采用综合计算和实验方法设计并验证了一种针对结直肠癌的新型多表位疫苗。通过计算机预测和优化最终构建,然后在CRC小鼠模型中进行重组表达和体内测试。接受多剂量疫苗的小鼠的平均肿瘤体积比未接受治疗的癌症组低约80%。此外,IL-4水平显著升高(p < 0.0001),与体液免疫应答的激活一致。组织病理学检查显示脾脏、肾脏和肝脏组织结构基本保留。多剂量疫苗组的存活率为100%,而未经治疗的癌症组的存活率为60%。这些结果表明,该疫苗可以抑制肿瘤进展,增强免疫反应,并提供全身保护,支持进一步的临床前开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design and in vivo evaluation of a multi-epitope vaccine that suppresses tumor growth in a murine colorectal cancer model.

Harnessing the immune system through cancer vaccines offers a promising strategy to overcome tumor heterogeneity, which remains one of the most significant challenges in achieving effective treatment for colorectal cancer (CRC). In this study, we designed and validated a novel multi-epitope vaccine against CRC using integrated computational and experimental approaches. The final construct was developed through in silico prediction and optimization, followed by recombinant expression and in vivo testing in a CRC mouse model. Mice receiving the multi-dose vaccine exhibited a mean tumor volume approximately 80% lower than that of the untreated cancer group. Additionally, IL-4 levels were significantly elevated (p < 0.0001), consistent with activation of humoral immune responses. Histopathological assessment showed largely preserved tissue architecture in the spleen, kidney, and liver. The multi-dose vaccine group achieved 100% survival, compared with 60% survival in the untreated cancer group. These results suggest the vaccine can suppress tumor progression, enhance immune responses, and provide systemic protection, supporting further preclinical development.

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来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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