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Use of Ly6K specific CAR T-cells to treat primary and metastatic triple negative breast cancer

使用 Ly6K 特异性 CAR T 细胞治疗原发性和转移性三阴性乳腺癌

基本信息

批准号：
10477934
负责人：
Geeta Upadhyay
金额：
$ 17.47万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
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：
2021-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10477934
关键词：
Adverse effects Affect Affinity Binding Biological Markers Blood Blood - brain barrier anatomy Brain Breast Cancer Cell Breast Cancer Model Breast cancer metastasis CD19 gene Cancer Cell Growth Cancer Center Cell Surface Proteins Cell Therapy Cell surface Cells Cessation of life Chimeric Proteins Clinical Trials Colon Carcinoma Data Defect Department of Defense Disease Disease remission Distant Metastasis Ensure Epidermal Growth Factor Receptor Estrogen Receptors Family member Female Future Generations Genes Growth Head Cancer Human Immune Immunotherapy In Vitro Incidence Infertility Knockout Mice Letters Lymphocyte antigen Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of lung Malignant neoplasm of ovary Malignant neoplasm of pancreas Malignant neoplasm of prostate Memory Metastatic Neoplasm to the Lung Modeling Monoclonal Antibodies Mus Neck Cancer Neoplasm Metastasis Normal Cell Organ Outcome Patients Progesterone Receptors Prognosis Proteins Proto-Oncogene Proteins c-akt Reproducibility Risk Signal Transduction Solid Spermatogenesis Surface T-Lymphocyte Testing Testis Transforming Growth Factor beta United States Woman Xenograft Model bone cancer cell cancer immunotherapy cancer recurrence cell motility chimeric antigen receptor chimeric antigen receptor T cells cytokine release syndrome effective therapy epithelial to mesenchymal transition experimental study genetically modified cells in vivo innovation knock-down male malignant breast neoplasm malignant stomach neoplasm migration mouse model new therapeutic target novel overexpression research clinical testing side effect sperm cell survival outcome therapeutic target triple-negative invasive breast carcinoma tumor tumor xenograft tumorigenesis vector

项目摘要

Project Summary/abstract We have identified that increased Ly6K expression is associated with poor outcome in triple negative breast cancer (TNBC). Mechanistically, Ly6K is required for the activation of TGFβ signaling and is increased in tumorigenesis in vivo. We propose that the biomarker Ly6K is an ideal therapeutic target for the treatment of TNBC because this protein is not expressed in normal cells, except in testis. Ly6K is also not required for vital organ function, except for spermatogenesis. Thus, targeting this protein for the treatment of TNBC, a disease affecting mostly females, is appropriate and ideal. Because of this, Ly6K is an optimal therapeutic target for TNBC immunotherapy using CAR T-cells. CAR T-cells are genetically modified T cells which express a chimeric antigen receptor fusion protein (CAR) derived from a monoclonal antibody (mAb) recognizing a target protein on the surface of cancer cells. CAR T-cells can recognize and kill target cells expressing the target protein without the need for HLA matching. We have generated three high affinity mAbs against human Ly6K, which recognize the cell surface Ly6K on cancer cells. The sequences from Ly6K mAbs were used to generate a CAR in a third generation lentiviral CAR vector to generate Ly6K-specific CAR T-cells. We will test whether Ly6K-specific CAR T-cells will recognize cancer cells expressing cell surface Ly6K and eliminate them in primary and metastatic TNBC mouse models.

项目总结/文摘