title: Infection-mimicking poly(γ-glutamic acid) as adjuvant material for effective anti-tumor immune response.
abstract: Bio-derived low molecular weight poly(γ-glutamic acid) (γ-PGA) was suggested as a novel adjuvant material for use in cancer vaccines. When the infection-mimicking γ-PGA was immunized with ovalbumin (OVA) as a model antigen, increase in the dendritic cell (DC)-mediated functions such as activation, maturation, antigen uptake, migration to lymph nodes, and priming of lymphocytes, which included cross-presentation, was observed. These DC-mediated functions were found to be facilitated by γ-PGA in a dose-dependent manner, with stimulation of toll-like receptor 4 (TLR4) being one of the underlying mechanisms. The in vivo efficacy of γ-PGA was tested in a mouse tumor model where both arms of adaptive immunity (humoral and cell-mediated) were found to be significantly enhanced in the presence of γ-PGA, indicating efficient priming of B and T cells. Moreover, immunization of mice with γ-PGA followed by EG7-OVA tumor challenge led to dramatic inhibition of tumor growth. After 71 days, the cured mice were rechallenged with tumor cells at a distant site in order to test the memory effect. No tumor growth was observed, which indicates the presence of a systemic, long-lasting immune response. Based on these results, low molecular weight γ-PGA is expected to have tremendous potential for applications in cancer immunotherapy.
authors.affiliation: Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Anushree
authors.initials: A
authors.lastname: Seth
authors.affiliation: Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Min Beom
authors.initials: MB
authors.lastname: Heo
authors.affiliation: Kookmin University and Bioleaders Corporation, Republic of Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Sung
authors.affiliation: SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: yongtaik@skku.edu.
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D045142:Cross-Priming / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007156:Immunologic Memory / Q000187:drug effects; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D016019:Survival Analysis; D018675:Toxicity Tests; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000941:Antigens; D000970:Antineoplastic Agents; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid
keywords: Adjuvant; Anti-tumor therapy; Dendritic cells