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Breast cancer virotherapy

乳腺癌病毒治疗

基本信息

批准号：
10358606
负责人：
BIN HE
金额：
$ 21.98万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10358606
关键词：
Antitumor Response Australia Biological Breast Cancer Model Breast Cancer therapy Cancer Etiology Cell Death Cell Maturation Cell Proliferation Cells Cessation of life Clinical Combination immunotherapy Combined Modality Therapy Coupled Dendritic Cells Development Disease Distant Early Diagnosis Early treatment Engineering Epigenetic Process Europe FDA approved Genes Genetic Genetic Engineering Genome Goals Herpes Simplex Infections Herpesviridae Herpesvirus 1 Human Immune Immune Targeting Immune response Immune system Immunologics Immunosuppression Individual Inflammation Inflammatory Interferons Knock-out Lobular Malignant Neoplasms Mammary Duct Mammary Neoplasms Mediating Metastatic to Mutation N-terminal Natural Immunity Nature Normal Cell Normal tissue morphology Oncogenes Oncolytic Oncolytic Immunotherapy Oncolytic viruses Pathway interactions Patients Periodicity Pre-Clinical Model Process Production Recombinants Recurrence Refractory Research Second Messenger Systems Signal Transduction Stimulator of Interferon Genes Survival Rate Switzerland Technology Therapeutic Treatment Efficacy Tumor Antigens Tumor Immunity Tumor Suppressor Genes Vertebral column Virus Virus Replication Woman Work anti-PD1 antibodies anti-cancer cancer cell cancer diagnosis cancer therapy chemokine cytokine design gene product immune checkpoint blockade immunogenic improved in vivo malignant breast neoplasm melanoma mouse model neoplastic cell novel oncolytic herpes simplex virus oncolytic virotherapy orthotopic breast cancer pre-clinical standard care synergism therapeutically effective tumor tumor microenvironment

项目摘要

Breast cancer is the most frequently diagnosed cancer in women worldwide. Despite advances in early detection and treatment, a notable fraction of patients progress to metastatic disease where no cure exists. Accordingly, there is a pressing need for effective therapeutic strategies. Breast cancer arises primarily due to genetic or epigenetic alterations that aberrantly regulate oncogenes, tumor-suppressor genes or immune genes. While advantageous for cancer cell proliferation or immune-escape, these changes often make malignant cells vulnerable to attack by oncolytic herpes simplex (HSV). There is now increased recognition that dynamic virus-host interplay determines the magnitude of cell destruction or release of immunogenic factors. Preliminary studies suggest that recombinant HSV that lacks selected gene motifs efficiently replicates in and lyses cancer cells. Furthermore, it activates dendritic cells that are necessary to mediate adaptive antitumor immunity. We hypothesize that selectively engineered HSV may serve as a distinct anticancer platform, which destructs malignant cells meanwhile primes superior antitumor immunity. With state of the art technology, we will determine the therapeutic potency of oncolytic HSV in preclinical models. As such, we will systematically examine the antitumor activities exerted by genetically modified HSV. To achieve therapeutic synergy, we will integrate cyclic GAMP synthase, a key factor of innate immunity, into the oncolytic virus backbone. In addition, we will characterize its oncolytic efficacy in combination with an immune checkpoint blockade. Lastly, we will investigate the nature by which oncolytic HSV remodels the tumor microenvironment for antitumor responses. Collectively, these studies may facilitate the development of novel agents for breast cancer therapy.

乳腺癌是全世界女性中最常见的癌症。