Strategies to treat solid tumors
Open AccessThe goal of this dissertation was to develop two treatment modalities for solid tumors: adoptive cell therapy and photothermal therapy. Adoptive cell therapies have yielded great success in liquid tumors but have faced challenges in treating solid tumors. Similarly, photothermal therapies against solid tumors have the potential to be effective but can also have off-target effects. In Chapters 2 and 3 of this dissertation, an adoptive cell therapy for mesothelioma was developed. NK cells were modified to be resistant to TGF-ß via expression of a TGF-ß dominant negative receptor II (DNR) and to secrete IL- 15. These modifications significantly increased NK cell clearance of solid tumor cells in vitro and in an in vivo xenograft model but caused severe acute toxicity that was not mitigated by steroid treatment or cryopreservation. In Chapter 4, the efficacy of heparanase in aiding NK cell invasion was examined as a potential method to augment the effectiveness of these cells as a cell therapy. Overall, exogenously-administered heparanase did not increase invasion except in some pretreatment and Prussian blue nanoparticle (PBNP)-conjugated conditions, though these increases were not significant. In Chapter 5, PBNPs were conjugated to an aFn14 antibody to enhance PBNP retention on Fn14-expressing glioblastoma cells for photothermal therapy. The antibody conjugate retained the PBNPs on the cells without greatly altering thermal and immunogenic cell death induced by PBNP-mediated photothermal therapy. Overall, this dissertation details potential methods to treat solid tumors: via adoptive cell therapy and, separately, via a PBNP-mediated photothermal therapy.
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