%0 Journal Article
%T Artificial T Cell Mimetics to Combat Melanoma Tumor Growth | Insight Medical Publishing
%A Amy Singleton
%A Biju Parekkadan
%A Dongli Guan
%A Matthew Li
%A Shilpaa Mukundan
%A Yunlong Yang
%J American Journal of Advanced Drug Delivery
%D 2018
%R 10.21767/2321-547X.1000023
%X Despite recent breakthroughs in melanoma treatment with anti-PD-1 immunotherapy, innovative approaches are needed to improve off-target effects. In this study, we report a T cell mimetic microparticle delivery of soluble PD1 aiming at providing a carrier substrate for future combinatorial and targeting efforts. Microparticles of sizes varying from (5 ¦Ìm to-7 ¦Ìm) were conjugated with soluble mouse or human PD-1 through nearly irreversible binding between streptavidin and biotin. PD-1 conjugated microparticles (PDMPs) suppressed 3-dimensional tumor growth of human A375 and mouse B16-F10 melanoma cells compared to control microparticles conjugated with the Fc portion of human IgG1 (IgG1MPs). This can be attributed to competitive inhibition by PDMPs on a melanoma cell-intrinsic PD-1/PD-L1 pathway. A single, local administration of mPDMPs in a B16-F10 mouse melanoma model inhibited tumor growth significantly compared to control IgMPs at the same dose. CD45+ immune cells were found to infiltrate tumors treated with mPDMPs as a mechanism for tumor control. These results collectively suggest that PDMPs can target the melanoma cell-intrinsic PD-1/PD-L1 pathway and that these artificial T cell mimetics can be the scaffold for further improvements in anti-tumor immunotherapy.
%U http://www.imedpub.com/articles/artificial-t-cell-mimetics-to-combat-melanoma-tumor-growth.php?aid=23050