Contents lists available at SclenceDireet RE Foy Biomaterials ELSEVIER journal homepage: www.elsevier.com/locate/biomaterials: Anticancer nanocage platforms for combined immunotherapy designed to harness immune checkpoints and deliver anticancer drugs In Seon Jeon®**', Jae Do Yoo*"**, Smriti Gurung“, Minseong Kim *""* Chanju Lee‘, Eun Jung Park“, Rang-Woon Park", Byungheon Lee *"*, Soyoun Kim“ * Department of Biohanisry and Cal Bil, Scho of Med, Kyungpook National Unters, 680 Gubchstosargro, Jung Daeg, 41944, Republic of Koren "BK! Pls KNU Biomedical Conveyence Praga, Department of Biome Scie, School of Mec, Kyungpook National Uiverty, 680 Gutchaeboarg ung, Dog, 41966, Repub of Korea * cats Seto of Medicine, Kyungpook National Unbenty, 680 Gukchaebosangro, ug gu, Daegu 41944, Repl of Korea «ance Inmunolgy Branch, Dison of Cancer BlamdialScnc, Graduate Shoo of Cancer Seance and Ply, Natonal Cancer Centr, Gayang, 10408, Repub of korea Presented By: Chloe Weyer & Shrey Patel April 22nd, 2021Motivation of Study Monoclonal ICBs are costly and often have systemic side effects Design a nanoparticle that utilizes specific targeting peptides for PD-L1 signal inhibition rather than antibodies that target PD-L1 Use ferritin, a naturally occurring compound, to minimize foreign body response Utilize nanoparticles as a chemotherapeutic drug delivery system while simultaneously inhibiting PD-L1(to induce increased immune response for solid tumors)Goal of Study e Design biocompatible nanocages decorated with PD-Lipep1 to act as an ICB e Encapsulate doxorubicin (Dox) within the cage for tumor-specific drug delivery 2% » % PD-L1 binding ~~ peptides (PD-L1pep) A * PD-Lipep nanocage (PpNF) PD-4+ PD-L1 Cancer pcue I cells: cells eo: Immune checkpoint blocking ‘+ chemotherapy chemotherapeutic drugs (Dox) Dox encapsulatedPpNF (PpNF-Dox)Biology Background e Programmed Death Ligand 1(PD-L1) induces apoptosis in T cells oe Sy o = e PD-L1is overexpressed on tumor cells as a means of evading the immune response Tumor Cell Teall Image retrieved from htps/ new genecopociacom/applications/pd-t-and-pd-i-targeting-sgrna-leniviral-partiles}Biomaterials Background e Plasmids were manufactured to include one of three modified ferritin gene encoding PD-L1 peptide (PD-Lipep1) * Bacteria were transformed with plasmid and cultured. Protein was harvested and purified; endotoxin removal was page performed to ensure purification quality (exastnne) * Refolding procedure induced protein self-assembly, allowing for downstream SDS-PAGE analysis.Nanocage Design A B ef @ Number (%) 34 woatm 2 aie €, a ‘Diameter (nim) Diameter (nm) Diameter (nm)cT26 MDA-MB 231Treatment Distribution A PpNF Control_wt Fortin” PBN LEPISD SL organsPD-L1 Antibody Treatment vs. Nanocage TreatmentIn Vivo Model T cell Populations Fea Ww oH ey ~~ .. *, ti us. Bs, € i Gg | € oo oo ES (9 80 1 +909 4009 +8909 (5001 esnog ora o3r09PpNEF Upregulates CD8 T Cell Response > og | See % %, F i 5Doxorubicin Combined Treatment Results A Cell viability (%) Pe mt > POL al oo Pon > Peete nn © bor 1000 = Ponrioon)Discussion and Conclusions e PD-Lipepi presenting ferritin nanocages specifically targets PD-L1 expressing tumor cells e PpNF(Dox) combination treatment was more effective in tumor reduction than anti-PDL1 antibody, suggesting that this may be a viable treatment option for solid tumor patientsFuture Directions e Try drug delivery system to deliver different types of chemotherapeutics e The overexpression of PD-L1 in renal cancer cells, which originate from tubular epithelial cells, suggests that PpNF may be a promising candidate for the treatment of patients with renal cell carcinoma. e This study suggests that combination therapy may be more efficient in solid tumor treatment than traditional ICBs alone.References 1. 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