Artificial T Cell Mimetics to Combat Melanoma Tumor Growth

Abstract

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 μm to-7 μm) 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.

Biomimetic and Materials-Potentiated Cell Engineering for Cancer Immunotherapy

“…Taking ad vantage of biomimetic materials, multiple immunosuppressive signals can be blocke Eventually, the immune tolerance of the TME is disrupted and the infiltration of immun cells increases. Mukundan et al reported a T cell mimic by constructing PD-1-conjugate microparticles (PDMPs) [21]. Unlike the antibody blockade, PDMPs could competitive In addition to directly killing tumor cells, T cell mimics could be fabricated as decoys to ameliorate immunosuppression and prevent excessive immune responses.…”

“…Eventually, the immune tolerance of the TME is disrupted and the infiltration of immune cells increases. Mukundan et al reported a T cell mimic by constructing PD-1-conjugated microparticles (PDMPs) [21]. Unlike the antibody blockade, PDMPs could competitively inhibit the PD-1/PD-L1 signaling, while maintaining normal immune tolerance and the CD45 + immune cell recruitment was enhanced with PDMPs treatment, which was a mechanism for tumor control.…”

Chemically Engineered Immune Cell‐Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools

“…Mukundan et al have recently introduced a novel TCmimicking microparticle to combat PD1 signaling. [257] To this end, streptavidin-coated polystyrene microparticles with the size of 5-7 µm were conjugated with biotinylated human or mouse PD1 as a competitive inhibitory strategy with the PD1 on the surface of the TCs. In vivo studies showed that when a single dose of the particles was injected directly in the tumor (but not intravenously) of the melanoma-bearing animals, a 4.6-fold decrease in the tumor volume was observed in the group receiving the PD1-decorated particles.…”