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Studying factors controlling cancer progression and immune recognition in mouse models

研究小鼠模型中控制癌症进展和免疫识别的因素

基本信息

批准号：
10707303
负责人：
TYLER E. JACKS
金额：
$ 93.49万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-20 至 2029-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10707303
关键词：
Antigens Area CRISPR/Cas technology Cancer Biology Cancer Control Cancer Model Cancer Patient Cancer Vaccines Cells Data Set Development Disease Progression Dissociation Evolution Foundations Functional disorder Gene Expression Genes Genetic Engineering Genetically Engineered Mouse Human Immune Immune system Immunotherapy In Situ Laboratories Lung Adenocarcinoma Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of pancreas Methods Modeling Molecular Nature Organoids Pancreatic Ductal Adenocarcinoma Pathway interactions Pre-Clinical Model Preventative vaccination Research Specimen System T cell response T-Cell Activation T-Lymphocyte Time Vaccine Therapy cancer cell cancer type cell type clinical translation experimental study genetic profiling genome editing human model improved mouse model novel novel therapeutic intervention response single cell analysis technology development tool transcriptomics tumor tumor microenvironment tumor progression vaccine strategy

项目摘要

Summary Over the past three decades, the Jacks laboratory has been a recognized leader in the development and characterization of genetically engineered mouse models of cancer, among other pre-clinical models. The laboratory has also studied human cancer specimens and datasets to validate finding from their experimental systems and to advance discoveries toward clinical translation. While Jacks laboratory has investigated many cancer types over time, this proposal is focused on models of lung adenocarcinoma and pancreatic ductal adenocarcinoma. By developing and deploying tools of genetic engineering and genetic profiling, such as CRISPR-based methods and single-cell analysis, the laboratory has pioneered new models and analytical approaches that have allowed for a deeper understanding of disease progression, including interactions between developing tumors and the immune system. This proposal builds on this foundation at the intersection of cancer biology and technology development to explore in detail the molecular and cellular aspects of tumor evolution. Single-cell profile methods will be augmented by spatial transcriptomics to characterize the changes in gene expression—in cancer cells as well as other cell types within the tumor microenvironment—in situ, rather than in dissociated cells. Genes and pathways implicated by this analysis will be subjected to functional analysis using organoid-based models as well as in the autochthonous setting. A second major theme of this proposal is the further exploration of tumor-immune interactions in lung cancer, which the laboratory has been studying for several years. Following up on experiments investigating the factors that control T cell activation and dysfunction in the setting of lung and pancreas cancer development, the laboratory will explore methods to provoke effective anti-tumor T cell responses as well as an improved response to immunotherapy. These studies will investigate the nature of the antigens and antigen combinations that induce effective T cell priming and activation, including through prophylactic and therapeutic vaccinations. Results of these experiments will inform new therapeutic approaches, including novel cancer vaccine strategies, in human cancer patients.

总结