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，化疗免疫治疗是恶性鳞癌患者的一线治疗方法。然而，晚期或复发的HNSCC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增强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种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。聚合物基纳米粒子被广泛认为是一种较好的纳米粒子体系，因为它们无毒且副作用小。该项目的目的是开发一种基于聚合物的纳米颗粒，用于递送佐剂（免疫激活剂）和抗原，并评估HNSCC小鼠模型的抗肿瘤免疫活性。在Sebastien Perrier教授的指导下，该学生（一年级）将设计聚合物纳米颗粒并在体外表征其性能。然后，在Shashi Prasad Rama博士的监督下，通过建立HNSCC小鼠模型和表征抗肿瘤免疫，将在体内（第2年和第3年）评估主要候选材料。学生将学习开发和表征聚合纳米颗粒的尖端工具，并进一步获得体内肿瘤动物模型的开发技能和各种分子生物学技术，如流式细胞术、ELISA和免疫组织化学等。该项目将以华威大学和大学医院为基地，高度跨学科，为学生从材料科学到临床前研究的培训提供良好的支持。

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.