Advanced Rigidity-based Material for Enhanced Immunotherapy

用于增强免疫治疗的先进刚性材料

• 批准号: 9182814
• 负责人: Lance C Kam
• 金额: $ 39.26万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9182814
• 关键词: Adaptive Immune System; Address; Adopted; Adoptive Immunotherapy; Alpha Cell; Animal Model; Animals; Antibodies; Area; Back; Biomedical Engineering; Bioreactors; CD28 gene; CD3 Antigens; Caliber; Cell Culture System; Cell Culture Techniques; Cell Differentiation process; Cell Proliferation; Cell Surface Receptors; Cells; Chemicals; Chemistry; Clinical; Clinical Trials; Complement; Data; Development; Dimensions; Disease; Elastomers; Electrospinning; Engineering; Fiber; Formulation; Goals; Gold; Growth; Human; Immobilization; Immune system; Immunology; Immunotherapy; Individual; Measures; Mechanics; Methodology; Morphology; Outcome; Patients; Phenotype; Polymers; Polystyrenes; Population; Process; Proteins; Protocols documentation; Research Personnel; Research Project Grants; SELL gene; Signal Transduction; Structure; Surface; System; T cell response; T-Cell Activation; T-Cell Proliferation; T-Lymphocyte; Techniques; Technology; Testing; Work; base; cancer therapy; cell type; cytokine; efficacy testing; improved; mechanical properties; nano; polydimethylsiloxane; programs; public health relevance; response; safety testing; therapy development; tool

DESCRIPTION (provided by applicant): The adaptive immune system is a powerful platform for development of targeted, robust, and persistent treatment of a range of diseases. A central step in many forms of adoptive T cell immunotherapy is the ex vivo expansion of a starting population of T cells. This project focuses on development of a new cell culture platform that will enhance the process of T cell expansion, leveraging the recent discovery that T cells are sensitive to the mechanical rigidity of the material presenting activating antibodies to CD3 and CD28, which provide antigenic and costimulatory signals, respectively. Specifically, T cell proliferation and retention of CD62L increased with decreasing stiffness of the support material. The goal of this proposed work is to transform the planar polydimethylsiloxane (PDMS) elastomer platform used in those initial studies into a system more compatible with contemporary T cell expansion; this is currently carried out using a polymer bead format to induce T cell activation. Specifically, we propose to develop, under the PAR-13-137 BRG program, a fiber-based format for PDMS that will offer enhances surface area for T cell stimulation in a compact volume that is also easy to incorporate into existing bioreactor systems. These studies are organized into three complementary Specific Aims: SA1) develop PDMS fibers into a cell culture format through the use of electrospinning, SA2) develop a chemical system for covalent immobilization of activating biomolecules onto the PDMS fibers, which would address anticipated regulatory and handling challenges, and SA3) determine the fiber morphologies and compositions that provide the best control over the number and phenotypic profile of cells generated using this platform. Successful completion of these studies will provide key information required for subsequent animal studies testing the safety and efficacy of T cells expanded using this platform.

描述（由申请人提供）：适应性免疫系统是开发针对一系列疾病的靶向、稳健和持久治疗的强大平台。在许多形式的过继性T细胞免疫治疗的中心步骤是体外扩增的起始群体的T细胞。这个项目的重点是开发一个新的细胞培养平台，将