Designing Biomaterials for Cancer Immunotherapy

Pin Wang

Department of Chemical Engineering and Materials Science, University of Southern California

Abstract:

Chimeric antigen receptors (CARs) are engineered artificial receptors composed of both target-recognition and T-cell activation functions. Once expressed in T lymphocytes, CARs can direct T cells to recognize tumor cells and mediate killing to eradicate the cancer. This type of “living drug” resulted in substantial and durable responses in a subset of patients with B cell malignancies treated with T cells engineered to express a CAR that targets the B cell-specific CD19 molecule. However, attempts to utilize CAR therapies for treatment of solid tumors have been less promising. In this talk, I will begin to present our own clinical experience on the CAR-T therapy for treating B cell malignancies and how costimulatory domains and conditions of cell manufacturing impact in vivo behaviors of CAR-T cells in patients. I will then present a series of strategies undertaken in my laboratory to confront the challenge of CAR-T therapy for solid tumors. One key example is the exploitation of nanoparticle formulation for delivering A2A adenosine receptor antagonists with the aim to modulating tumor microenvironment (TME). We found that small molecular inhibitors can be delivered to the TME by nanoparticles and can efficiently block adenosine signaling. Such a blockade can disrupt adenosine-mediated immunosuppression in the TME and create favorable conditions for infused CAR-T cells to overcome physical barriers and actively infiltrate into the tumor milieu. In addition, CAR-T cells can maintain their biological functions under this blocked environment and are more efficient to mediate antitumor immune responses. 

报告时间：6月30日上午10:00

报告地点：环资楼939会议室

王品，博士，教授

中国科技大学生物学学士（材料科学与工程系1992级），加州理工大学化学工程博士、博士后， 美国南加州大学工程学院化工及材料科学系、生物医学工程系、及药学系教授，Zohrab A. Kaprielian冠名讲座教授。王品教授是国际著名的生物工程及医学材料专家，在免疫调控和靶向基因及药物传递的工程改造方向的研究居于世界领先水平。作为通讯作者，先后在Nature Biotechnology，P.N.A.S，Nano Letter， ACS Nano，Gene Therapy，Human Gene Therapy，Molecular Therapy，J.A.C.S，Pharmaceutical Research，Vaccine，Biomaterials，Molecular Pharmaceutic 等国际顶级杂志发表90多篇论文，和六项已获美国国家专利局批准的专利。其实验室构建的DC细胞靶向的慢病毒载体体系已经在一个一期临床中得到应用（临床项目：NCT02122861). 在转化医学研究领域上，王品教授主要集中在针对免疫生物工程的新技术开发以及在肿瘤免疫治疗中的应用。王品教授是南加大免疫生物工程中心的主任，带领团队开发新型肿瘤疫苗载体与相应的临床试验；设计和工程新一代具备智慧型功能的嵌合抗原T (CAR-T) 细胞来提高肿瘤免疫疗法的安全和有效性；探索如何利用工程改造的免疫细胞实现更有效的药物传递；并开发新工艺来实现更有效工业规模的病毒载体和免疫细胞的生产。