疫苗设计可以显着改善癌症免疫疗法

StephenW

                    Vaccine Design Can Dramatically Improve Cancer Immunotherapies                                                    News   May 07, 2019 | Original story by Amanda Morris, Northwestern University               
               
                             The most effective spherical nucleic acid-based vaccine for cancer immunotherapy featured a peptide antigen (in green) interspersed with DNA. Image credit: Northwestern University
                                    
                    
               
                                                   
When it comes to the effectiveness of nanotherapeutic vaccines, shape matters.

A Northwestern University team investigated a set of spherical nucleic acids (SNAs) for their potential to stimulate cancer-quelling immune responses. After comparing a series of compositionally identical yet structurally different vaccines by testing them on multiple animal models, the researchers found the structure of SNAs in one vaccine dramatically outperformed the others, which ranged from ineffective to nearly curative.

Vaccines with the superior structure completely eliminated tumors in 30% of animals and improved their overall survival from cancer. The vaccine also protected the animals from reemerging tumors.
“This observation shows the importance of chemical structure and three-dimensional presentation of active components in the design of vaccines,” said Northwestern’s Chad A. Mirkin, who co-led the study. “This information will help us rationally design SNA vaccines that can raise the strongest possible anti-cancer immune responses. Having a clear design strategy also will accelerate the development of vaccines for many types of cancer and potentially other diseases.”

The study will be published online during the week of May 6 in the Proceedings of the National Academy of Sciences.

Mirkin is the George B. Rathmann Professor of Chemistry in Northwestern’s Weinberg College of Arts and Sciences and director of the International Institute for Nanotechnology. He co-led the study with Bin Zhang, professor of medicine and microbiology-immunology at the Northwestern University Feinberg School of Medicine, and Andrew Lee, research assistant professor of chemical and biological engineering in Northwestern’s McCormick School of Engineering.

Cancer immunotherapies artificially stimulate the patient’s immune system to find and attack the disease. So far, new immunotherapies, called checkpoint inhibitors, act by unlocking immune responses that are suppressed by tumors. But they are effective only in certain types of cancer and in a fraction of patients.

“Another potentially more powerful approach is to raise and boost immune responses with therapeutic vaccines,” Lee said. “This approach, however, has needed breakthroughs in vaccine design to unlock its potential in treating cancer in the clinic.”

The development of SNAs could be the breakthrough for which people have been waiting. Invented by Mirkin, SNAs are synthetic globular — rather than linear — forms of DNA and RNA that surround a nanoparticle core. Roughly 50 nanometers in diameter, the tiny structures possess the ability to enter cells, including immune cells, for targeted treatment delivery.

In the study, the Northwestern team compared SNAs that have different structures but the same peptides, DNA and other general components. All vaccines included an antigen (a substance that is recognized and targeted by an immune response) and an adjuvant (a substance that enhances the body’s immune response to the antigen). In this case, the DNA is the adjuvant, and the peptide is the antigen.

The only thing that changed in each vaccine was the position of the peptide antigen, which was either housed in the core of the SNA, interspersed with the DNA or attached to the DNA. These changes led to major differences in how the immune system recognized and processed molecular cues, ultimately affecting the quality of the immune response generated by the vaccine. In the study, the peptide antigen interspersed with the DNA performed best.

“The study shows that SNAs and our ability to refine SNA structures can dramatically improve the anti-tumor immune responses,” Zhang said. “This shows promise in our ability to improve the performance of vaccines and eventually use them in patient care.”

This article has been republished from materials provided by Northwestern University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

The study, "Rational vaccinology with spherical nucleic acids" will be published online during the week of May 6 in the Proceedings of the National Academy of Sciences.

StephenW

疫苗设计可以显着改善癌症免疫疗法

新闻2019年5月7日|西北大学Amanda Morris的原创故事

疫苗设计可以显着改善癌症免疫疗法

用于癌症免疫疗法的最有效的基于球形核酸的疫苗的特征在于散布有DNA的肽抗原（绿色）。图片来源：西北大学

当谈到纳米治疗疫苗的有效性时，形状就很重要。

西北大学的一个研究小组调查了一组球形核酸（SNAs），它们具有刺激癌症免疫反应的潜力。通过在多种动物模型上测试一系列成分相同但结构不同的疫苗后，研究人员发现一种疫苗中SNA的结构明显优于其他疫苗，其范围从无效到接近治愈。

具有优越结构的疫苗完全消除了30％的动物的肿瘤并提高了它们从癌症中获得的总体存活率。疫苗还保护动物免于重新出现肿瘤。

“这一观察结果显示了化学结构的重要性以及活性成分在疫苗设计中的三维呈现，”西北大学的Chad A. Mirkin说，他是该研究的共同领导者。 “这些信息将有助于我们合理地设计可以提高最强可能的抗癌免疫反应的SNA疫苗。制定明确的设计策略也将加速开发针对多种癌症和其他疾病的疫苗。“

该研究将于5月6日在美国国家科学院院刊上在线发表。

Mirkin是西北大学Weinberg艺术与科学学院的George B. Rathmann化学教授，也是国际纳米技术研究所所长。他与西北大学Feinberg医学院医学和微生物学 - 免疫学教授张斌和西北麦考密克工程学院化学和生物工程研究助理教授Andrew Lee共同领导了这项研究。

癌症免疫疗法人为地刺激患者的免疫系统以发现和攻击疾病。到目前为止，新的免疫疗法，称为检查点抑制剂，通过释放被肿瘤抑制的免疫反应起作用。但它们仅对某些类型的癌症和一小部分患者有效。

“另一个可能更强大的方法是用治疗性疫苗提高和增强免疫反应，”Lee说。 “然而，这种方法需要在疫苗设计方面取得突破，以释放其在临床治疗癌症方面的潜力。”

SNA的发展可能是人们一直在等待的突破。由Mirkin发明的SNAs是合成的球状 - 而非线性 - 围绕纳米粒子核心的DNA和RNA形式。这种微小的结构直径大约50纳米，具有进入细胞（包括免疫细胞）的能力，可用于靶向治疗。

在该研究中，西北大学的研究小组比较了具有不同结构但具有相同肽，DNA和其他一般成分的SNA。所有疫苗都包括抗原（一种被免疫反应识别和靶向的物质）和一种佐剂（一种增强机体对抗原的免疫反应的物质）。在这种情况下，DNA是佐剂，肽是抗原。

在每种疫苗中唯一改变的是肽抗原的位置，其位于SNA的核心中，散布在DNA中或附着在DNA上。这些变化导致免疫系统识别和处理分子线索的方式存在重大差异，最终影响疫苗产生的免疫应答的质量。在该研究中，散布有DNA的肽抗原表现最佳。

“这项研究表明，SNA和我们改善SNA结构的能力可以显着改善抗肿瘤免疫反应，”张说。 “这显示出我们改善疫苗性能并最终将其用于患者护理的能力。”

本文由西北大学提供的资料重新发表。注意：材料可能已根据长度和内容进行了编辑。有关详细信息，请与引用的来源联系。

参考：

该研究“球形核酸的合理疫苗学”将于5月6日在美国国家科学院院刊上在线发表。

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