title: Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma.
abstract: Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb). The combination of antigen-specific aAPC-based activation and anti-PD-1 mAb checkpoint blockade induced the greatest IFN-γ secretion by CD8+ T cells in vitro. Combination treatment also acted synergistically in an in vivo murine melanoma model to result in delayed tumor growth and extended survival, while either treatment alone had no effect. This was shown mechanistically to be due to decreased PD-1 expression and increased antigen-specific proliferation of CD8+ T cells within the tumor microenvironment and spleen. Thus, biomaterial-based therapy can synergize with other immunotherapies and motivates the translation of biomimetic combinatorial treatments.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Kosmides
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Meyer
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Hickey
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
authors.forename: K
authors.initials: K
authors.lastname: Aje
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Cheung
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Materials Science and Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Green
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.|Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Schneck
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D058045:Artificial Cells / Q000276:immunology*; D040761:Biomimetic Materials / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004343:Drug Implants / Q000008:administration & dosage; D004357:Drug Synergism; D019344:Lactic Acid / Q000737:chemistry; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D004343:Drug Implants; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Artificial antigen presenting cell; CD8+ T-cell; Combination therapy; Immunotherapy; PD-1