Janus particles designed for cancer immunotherapy

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Campbell, Elizabeth
Sulchek, Todd A.
Botchwey, Edward A.
Kwong, Gabriel A.
Roy, Krishnendu
Waller, Edmund
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Although CD8+ T cells commonly migrate to solid tumors, cancer cells suppress and evade these cells through a variety of intrinsic and extrinsic mechanisms. As a result, recruited cytotoxic T cells are rendered anergic or apoptotic and are thus ineffective at killing cancer cells. Cancer is traditionally treated using chemotherapy, radiation, and surgery; however, these treatments are often unsuccessful alone and are usually used in some combination – resulting in numerous side effects. Bispecific antibody therapy, in which a fusion protein contains antibody regions that target cancer cells and activate immune cells, has shown great promise but only a subset of cancer patients respond to treatment due to lack of avidity and the inflexibility of the design. Our lab has pioneered the engineering and application of a novel particle platform, called Janus particles, in which each particle hemisphere is functionalized specifically such that the particle is capable of two distinct biological functions. Thus the objective of this thesis overall was to develop a Janus particle-based cancer immunotherapeutic strategy that is capable to binding and activating CD8+ T cells while simultaneously targeting cancer cells. We characterized our the ability to activate T cells via biological and mechanical behaviors exhibited by dosed T cells and investigated the effect Janus particles have on eliciting cytotoxicity using 2D and 3D ovarian cancer cultures.
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