Improving the therapeutic immunity of cancer vaccine with multi-adjuvant polymeric nanoparticles

头颈部鳞状细胞癌(HNSCC)是一种侵袭性癌症，占头颈部所有癌症的90%。目前，化疗免疫疗法被用作HNSCC患者的一线治疗方法。然而，晚期或复发的HNSCC肿瘤患者对这种治疗的反应很差，因此需要开发一种新的策略来提高HNSCC肿瘤对当前免疫治疗的反应性。与传统的递送技术相比，基于纳米技术的癌症疫苗提供了一个宝贵的工具来定制癌症疫苗，以产生针对癌细胞的强大的抗肿瘤免疫反应。基于聚合物的纳米颗粒被广泛认为是一种更好的纳米颗粒系统，因为它们无毒且副作用较小。本项目的目的是开发一种基于聚合物的纳米颗粒，用于输送佐剂(免疫激活剂)和抗原，并评估其在HNSCC小鼠模型中的抗肿瘤免疫活性。在塞巴斯蒂安·佩里尔教授的指导下，这名一年级的学生将设计聚合物纳米颗粒，并在体外表征它们的性质。然后，在Shashi Prasad Rama博士的监督下，将通过建立HNSCC小鼠模型和表征抗肿瘤免疫来在体内(第二年和第三年)评估候选铅材料。学生将学习开发和表征聚合物纳米颗粒的尖端工具，并进一步获得开发体内肿瘤动物模型和各种分子生物学技术的技能，如流式细胞仪、ELISA和免疫组织化学等。这个项目将是高度多学科的，总部设在华威大学和大学医院，为学生从材料科学到临床前研究的培训提供极好的支持。

Head and neck squamous cell carcinoma (HNSCC) are an aggressive form of cancer attributes to 90% of all cancers in the head and neck area. Currently, chemo-immunotherapy is used as first line treatment for HNSCC patients. However, patients with advanced or recurrent HNSCC tumors respond poorly to this treatment, and there is therefore a need to develop a novel strategy to enhance the responsiveness of the HNSCC tumors to the current immunotherapy. Nanotechnology-based cancer vaccines offers an invaluable tool to tailor cancer vaccines to generate robust antitumor immune response against cancer cells in comparison to conventional delivery techniques. Polymer based nanoparticles are widely considered as better a nanoparticle system since they are non-toxic and have less side effects. The aim of this project is to develop a polymer-based nanoparticles for the delivery of adjuvants (immune activators) and antigens and assess the antitumor-immune activity in the HNSCC mouse model. Under the guidance of Prof. Sebastien Perrier, the student (year 1) will design the polymeric nanoparticles and characterize their properties in vitro. Then, under the supervision of Dr. Shashi Prasad Rama, lead material candidates will be assessed in vivo (year 2 and 3), by developing HNSCC mouse models and characterizing the antitumor immunity. The students will learn about cutting edge tools to develop and characterize polymeric nanoparticles and further will gain skills on development of in vivo tumor animal models and various molecular biology techniques such as flow cytometry, ELISA, and immunohistochemistry etc. This project will be highly multidisciplinary, being based both at the University of Warwick and the University Hospital and provide an excellent support for the training of a student from materials science to preclinical research.