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Full-Text Articles in Medicine and Health Sciences
A Novel Immunostimulatory Platform For Amplifying The Abscopal Response Rates Of Radiation Therapy, Patrick A. Paez
A Novel Immunostimulatory Platform For Amplifying The Abscopal Response Rates Of Radiation Therapy, Patrick A. Paez
Theses and Dissertations
Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50-60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regimens have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. …
Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne
Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne
Theses and Dissertations
Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …
Treatment-Induced Breast Cancer Dormancy And Relapse, Rebecca Keim
Treatment-Induced Breast Cancer Dormancy And Relapse, Rebecca Keim
Theses and Dissertations
When breast tumor cells encounter stress due to cancer therapies, they may enter a dormant state, escaping from treatment-induced apoptosis. Dormant cells may eventually regain proliferative capabilities and cause recurrent metastatic disease, which is the leading cause of mortality in breast cancer patients. We sought to determine if a high dose of radiation therapy (RT) or combined chemo-immunotherapy, with and without the blockade of autophagy by chloroquine (CQ), could overcome treatment-induced tumor dormancy or relapse. We found that autophagy contributes in part to treatment-induced tumor dormancy. We also found that three therapeutic strategies were successful in inhibiting or preventing tumor …
Ex Vivo Reprogramming Of Tumor-Reactive Immune Cells From Fvbn202 Mice Bearing Lung Metastatic Mammary Carcinoma: An Immunotherapeutic Opportunity Revealed Against Recurrence, Charles Hall
Theses and Dissertations
Metastatic breast cancer treatment has seen few advances in recent years, yet treatment resistance continues to rise, causing disease recurrence. A pilot study was performed to determine the efficacy of ex vivo expansion and reprogramming of tumor-reactive immune cells from experimental metastatic tumor-sensitized mice. Also, phenotypic changes in tumors due to metastasis or tumor microenvironment influences were characterized. Metastatic neu+ mouse mammary carcinoma (mMMC) and its distant relapsing neu-antigen-negative variant (mANV) were investigated in FVBN202 mice. Tumor-reactive central memory CD8+ T cells and activated NK/NKT cells were successfully reprogrammed and expanded during 6-day expansion from mMMC- and/or mANV-sensitized mice, resulting …
The Role Of Myeloid-Derived Suppressor Cells In The Immunotherapy Of Breast Carcinomas, Johanna Morales
The Role Of Myeloid-Derived Suppressor Cells In The Immunotherapy Of Breast Carcinomas, Johanna Morales
Theses and Dissertations
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells at various stages of differentiation. These cells are broadly characterized by the simultaneous expression of the surface markers CD11b and Gr1 and have been found to accumulate in large numbers in response to many different tumors in both mice and humans, including HER2/neu+ breast cancers. The adoptive immunotherapy of cancers has been a promising field, yet the clinical efficacy of adoptive immunotherapies targeted against human breast cancers and many other cancers has been extremely limited. Given the influx of MDSC in tumor-bearing individuals, we hypothesized that these cells were …