title: Adjuvant-Loaded Subcellular Vesicles Derived From Disrupted Cancer Cells for Cancer Vaccination.
abstract: Targeted subunit vaccines for cancer immunotherapy do not capture tumor antigenic complexity, and approaches employing tumor lysate are often limited by inefficient antigen uptake and presentation, and low immunogenicity. Here, whole cancer cells are processed to generate antigen-rich, membrane-enclosed subcellular particles, termed "reduced cancer cells", that reflect the diversity and breadth of the parent cancer cell antigen repertoire, and can be loaded with disparate adjuvant payloads. These vesicular particles enhance the uptake of the adjuvant payload, and potentiate the activation of primary dendritic cells in vitro. Similarly, reduced cancer cell-associated antigens are more efficiently presented by primary dendritic cells in vitro than their soluble counterparts or lysate control. In mice, vaccination using adjuvant-loaded reduced cancer cells facilitates the induction of antigen-specific cellular and humoral immune responses. Taken together, these observations demonstrate that adjuvant-loaded reduced cancer cells could be utilized in cancer vaccines as an alternative to lysate.
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Cheung
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.|Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA.
authors.forename: Sandeep T
authors.initials: ST
authors.lastname: Koshy
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Stafford
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.|Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
authors.forename: Maartje M C
authors.initials: MM
authors.lastname: Bastings
authors.affiliation: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D004337:Drug Carriers; D007111:Immunity, Cellular; D051379:Mice
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D004337:Drug Carriers
keywords: cancer cell vesicles; cancer vaccines; drug carriers; immunotherapy; lysate