CORE SUPPORT FOR THE IMMUNE CELL NETWORK

免疫细胞网络的核心支持

• 批准号: 10502596
• 负责人: ETHAN DMITROVSKY
• 金额: $ 584.25万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-16 至 2025-09-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10502596
• 关键词: Address; Adoptive Cell Transfers; Allogenic; Animal Model; Autologous; Biological Assay; Cell Therapy; Cells; Cellular immunotherapy; Chemotherapy and/or radiation; Clinical; Clinical Trials; Collaborations; Complex; Credentialing; Cyclic GMP; Dendritic Cells; Discipline; Engineering; Ensure; Fostering; Funding; Hematologic Agents; Hematologic Neoplasms; Hematopoietic stem cells; Human; Immune; Immunotherapy; Institution; Lymphocyte; Malignant Neoplasms; Mesenchymal; Mesenchymal Stem Cells; Multi-site clinical study; Multiple Myeloma; Normal tissue morphology; Patients; Pharmaceutical Preparations; Radiation induced damage; Research; Research Personnel; Resources; Safety; Science; Solid Neoplasm; Standardization; Study models; T-Cell Receptor; T-Lymphocyte; Therapeutic; Tissues; Tumor-Infiltrating Lymphocytes; United States National Institutes of Health; Work; cancer therapy; cell type; chimeric antigen receptor T cells; clinical application; clinical efficacy; clinical research site; engineered T cells; fitness; high standard; induced pluripotent stem cell; innovation; leukemia/lymphoma; macrophage; manufacturing process; member; novel; paracrine; pilot trial; preservation; rare cancer; stem cell therapy; success; tissue stem cells; tumor

The engineering of autologous or allogenic cells for clinical application has accelerated in recent years, to a point where significant successes have been observed with treatments for cancer and tissue damage from radiation and chemotherapy. Many cell types may be utilized including hematopoietic stem cells, induced pluripotent stem cells (iPSC), lymphocytes, dendritic cells, mesenchymal stem cells, and others. Cell-based immunotherapies have been particularly successful. There are approved agents for hematologic malignancies such as leukemia, lymphoma and myeloma; promising work is also being conducted to treat solid tumors. However, there remain significant scientific, technical, clinical, and regulatory challenges to bringing this powerful therapeutic strategy into widespread, effective clinical use. Investigators are just beginning to develop constructs that effectively destroy tumors while preserving normal tissue. Technical challenges include the complex manufacturing process used to make patient-specific final products from unique patient-specific starting materials or allogenic products that do not trigger an immune rejection. Standardized analytical assays must be developed to fully characterize cell products before and after these ‘living drugs’ are administered to patients and animal model studies may not be predictive. Furthermore, many therapeutic indications are for rare cancers or for those subtypes with small number of patients making it impossible to accrue statistically significant trial subjects at a single clinical site. As cell therapy science advances, there must also be an associated advancement in regulatory science to ensure that both quality and safety conform to the highest standards. Currently, no single institution is equipped to address all the hurdles that exist in the cell therapy field. The NCI seeks to provide core support for members of an Immune Cell Network (ICN). The ICN will consist of NIH-funded Centers that foster new discoveries, support strong collaborations across scientific, clinical, and regulatory disciplines, and make their own resources available across the network to advance the application of cell therapies produced under cGMP conditions for clinical trials. Each center will conduct research on one or more cancers using an adoptive cell therapy approach. The research consists of selecting a credentialed target for a specific cancer, interrogating therapeutic mechanism(s) of action, determining therapeutic cell fitness and persistence, and assessing clinical efficacy in human trials of novel cell therapy products. Specific cellular therapies supported may include immunotherapies [chimeric antigen receptor (CAR) T-cells, tumor-infiltrating lymphocytes (TIL), engineered T cell receptor (TCR)-T cells, natural killer (NK), dendritic cell (DC), and macrophage (MΦ)]; stem cell therapies (engineered iPSC, tissue stem cells, hematopoietic progenitors); and paracrine-acting cells (engineered mesenchymal cells). The centers will manufacture cell therapy products onsite for their own pilot trials and collaborate scientifically in multisite clinical studies to bring forward the most innovative ideas rapidly.

近年来，用于临床应用的自体或同种异体细胞的工程已经加速，在治疗癌症和放射和化疗引起的组织损伤方面取得了重大成功。许多细胞类型可以被利用，包括造血干细胞、诱导多能干细胞（iPSC）、淋巴细胞、树突状细胞、间充质干细胞等。