Year: 2010
Type: dissertation
Abstract: In the year 1971 U.S. President Nixon signed the "National Cancer Act" and thus declared a "war on cancer". Unfortunately, about 40 years later in 2009, U:S: pesident Barack Obama had to renew this declaration, since in 2007 still about 13% of all human deaths were caused by cancer. Standard therapies for most cancer types are surgery, hormone-, chemo- or radiotherapy, associated with severe side effects but, unfortunately in most cases, only limited success. The idea of immunotherapy, that means therapy of cancer via activation of CD4+ T cells, B cells and / or cytotoxic T cells responses against a tumor specific antigen, is promising, but up to date not very effective. In order to circumvent labor or cost intensive approaches it is necessary to target dendritic cells in vivo. They are professional antigen presenting cells, with the ability to present engulfed antigens in the context of co-stimulatory molecules, and thereby efficiently activating cytotoxic T lymphocytes. Biodegradable PLGA-microspheres (MS) are a potent tool to opsonize encapsulated antigens and immunostimulatory molecules for uptake by dendritic cells. Here we investigated, how this approach could be further improved in order to fulfill the requirements for clinical use. Chapter II deals with the characterization of PLGA-MS in the therapy of tumors in the mouse model and compares PLGA-MS with incomplete Freund s adjuvant (IFA). It could be shown that PLGA-MS possess a variety of valuable features and compare favorably to the gold-standard IFA. Chapter III and IV investigate CD1d ligands for their properties to serve as stimulatory and regulatory modulators in combination with the PLGA-MS system. Chapter V puts our previous findings in a more clinically relevant context, by using tumor cell line lysate as an antigen. Tumor lysate is a source of a variety of tumor antigens, which is easily accessible, e.g., after surgery of tumors. In general, PLGA-MS emerge as a flexible, powerful tool for immunotherapy, which might serve the desperate need for a contemporary in vivo antigen delivery device.
Source: KOPS (University of Konstanz)
Author: Marc Ulrich Müller
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W67511292