TitlePolymer based immune modulation for the generation of an anti-tumor immune response
NameNikitczuk, Kevin P. (author), Yarmush, Martin (chair), Schloss, Rene (internal member), Roth, Charles (internal member), Lattime, Edmund (outside member), Rutgers University, Graduate School - New Brunswick,
Polymeric drug delivery systems,
DescriptionIncreasing emphasis is being placed on overcoming tumor-associate immune escape mechanisms that facilitate disease progression. Understanding this immune tolerance and developing methods to overcome it provide advanced understanding to further develop vaccine strategies. In the current work we have engineered a polymer based therapy that enhances cellular immunity capable of generating anti-tumor activity. We have determined that a poly(lactic-co-glycolic acid) (PLGA) based delivery system encapsulating tumor associated antigen (ovalbumin, OVA) and the TLR9 agonist CpG motif DNA can initiate an effective type 1 mediated response. Local administration of the polymer therapy on E.G7-OVA lymphoma bearing mice significantly delayed tumor progression by eliciting a strong local and systemic IFN-γ mediated anti-tumor response. It was found that this response worked independently of antigen specific CTLs, which were active in the tumor draining lymph nodes yet incapable of retarding tumor formation. In analyzing the dendritic cell response to this polymer system, it was demonstrated that this delivery system indeed increased the Th1 phenotype of dendritic cells as measured by an increase in cell surface expression of CD80, CD86 and MHCII and secretion of the cytokines IL-12 and IFN-γ. In addition, introducing the immune modulator 1-Methyl Tryptophan (1-MT) in concert with the antigen and adjuvant enhanced the dendritic cell Th1 profile when delivered via the PLGA vesicle. Taken together, these studies demonstrate the immunological mechanisms and benefits of a PLGA based delivery system.
NoteIncludes bibliographical references
Noteby Kevin P. Nikitczuk
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.