title: Modular Three-component Delivery System Facilitates HLA Class I Antigen Presentation and CD8(+) T-cell Activation Against Tumors.
abstract: Cell-mediated immunotherapies have potential as stand-alone and adjuvant therapies for cancer. However, most current protocols suffer from one or more of three major issues: cost, safety, or efficacy. Here we present a nanoparticle delivery system that facilitates presentation of an immunogenic measles antigen specifically in cancer cells. The delivery system does not contain viral particles, toxins, or biologically derived material. Treatment with this system facilitates activation of a secondary immune response against cancer cells, bypassing the need to identify tumor-associated antigens or educate the immune system through a primary immune response. The delivery system consists of a stealth liposome displaying a cancer-specific targeting peptide, named H1299.3, on its exterior surface and encapsulating H250, an immunogenic human leukocyte antigen class 1 restricted peptide. This targeted-nanoparticle facilitates presentation of the H250 peptide in major histocompatibility complex class I molecules. Activation is dependent on the targeting peptide, previous antigen exposure, and utilizes a novel autophagy-mediated mechanism to facilitate presentation. Treatment with this liposome results in a significant reduction of tumor growth using an aggressive LLC1 model in vaccinated C57BL/6 mice. These data provide proof-of-principle for a novel cell-mediated immunotherapy that is scalable, contains no biologically derived material, and is an efficacious cancer therapy.
authors: SRI International, Bioscience Division, Macromolecular Sciences, Harrisonburg, Virginia, USA; UT Southwestern Medical Center, Dallas, Texas, USA.
authors: Benjamin J
authors: BJ
authors: Umlauf
authors: SRI International, Bioscience Division, Macromolecular Sciences, Harrisonburg, Virginia, USA.
authors: Chin-Ying
authors: CY
authors: Chung
authors: SRI International, Bioscience Division, Macromolecular Sciences, Harrisonburg, Virginia, USA. Electronic address: Kathlynn.Brown@sri.com.
authors: Kathlynn C
authors: KC
authors: Brown
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008458:Measles Vaccine / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000628:therapy*; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D008081:Liposomes; D008458:Measles Vaccine