Development and Characterization of an Autologous Whole Cell Breast Cancer Vaccine
type: CreativeWork
description: Approximately 40,000 women will die from breast cancer in the United States in 2014. About 90% of these deaths will be due to metastases, rather than the primary tumor and majority of metastases are due to the recurrence and progression of non-metastatic disease. Current adjuvant treatments, such as chemotherapy and radiation, have severe side effects and may result in overtreatment and drug resistance. Since greater than 90% of patients are diagnosed between stages I-III and have minimal residual disease after treatment, there is an opportunity to treat patients with an autologous breast cancer vaccine. Autologous vaccines under development have a multivalent antigen repertoire, nontoxic side effects and most importantly, allow for personalized, patient specific treatment. A vaccine may be able to eliminate remaining tumor cells following primary treatment, prevent a recurrence and result in improved survival. We developed an autologous breast cancer vaccine using two murine cell lines, 4T1 and EMT6, to demonstrate the potential of vaccines for adjuvant treatment of breast cancer. We first tested two commonly used methods of inactivating cells, irradiation and freeze/thaw cycling, to see if either method was superior in establishing protective immunity. Next, we measured surface expression of MHC I, MHC II, Fas, ICAM-1, B7-1 and B7-2 and secretion of the immunosuppressive cytokines GM-CSF, IL-6, MCP-1, TGF-β, and VEGF by each cell line to better understand differences in immunogenicity. In the EMT6 model, vaccination with irradiated cells provided protection from live tumor challenge in 80% of mice, while no protection was seen following vaccination with freeze/thawed cells. Furthermore, a minimum threshold of 250,000 irradiated cells was needed to elicit an anti-tumor response. In the 4T1 model, no protection was generated by irradiated or freeze/thawed vaccines. After measurement of surface molecules, B7-1 was up-regulated following irradiation in EMT6 cells, but…
abstract: Approximately 40,000 women will die from breast cancer in the United States in 2014. About 90% of these deaths will be due to metastases, rather than the primary tumor and majority of metastases are due to the recurrence and progression of non-metastatic disease. Current adjuvant treatments, such as chemotherapy and radiation, have severe side effects and may result in overtreatment and drug resistance. Since greater than 90% of patients are diagnosed between stages I-III and have minimal residual disease after treatment, there is an opportunity to treat patients with an autologous breast cancer vaccine. Autologous vaccines under development have a multivalent antigen repertoire, nontoxic side effects and most importantly, allow for personalized, patient specific treatment. A vaccine may be able to eliminate remaining tumor cells following primary treatment, prevent a recurrence and result in improved survival. We developed an autologous breast cancer vaccine using two murine cell lines, 4T1 and EMT6, to demonstrate the potential of vaccines for adjuvant treatment of breast cancer. We first tested two commonly used methods of inactivating cells, irradiation and freeze/thaw cycling, to see if either method was superior in establishing protective immunity. Next, we measured surface expression of MHC I, MHC II, Fas, ICAM-1, B7-1 and B7-2 and secretion of the immunosuppressive cytokines GM-CSF, IL-6, MCP-1, TGF-β, and VEGF by each cell line to better understand differences in immunogenicity. In the EMT6 model, vaccination with irradiated cells provided protection from live tumor challenge in 80% of mice, while no protection was seen following vaccination with freeze/thawed cells. Furthermore, a minimum threshold of 250,000 irradiated cells was needed to elicit an anti-tumor response. In the 4T1 model, no protection was generated by irradiated or freeze/thawed vaccines. After measurement of surface molecules, B7-1 was up-regulated following irradiation in EMT6 cells, but…
author: Kurtz, Samantha Leigh
keywords: Immunity, Molecular, Cellular, and Tissue Engineering, Oncology, Pharmacology
date published: 2014-12-01T08:00:00Z
date modified: 2026-07-24T00:58:44Z
provider: University of Arkansas
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Arkansas