title: EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor.
abstract: The prognosis of liver cancer remains poor, but recent advances in nanotechnology offer promising possibilities for cancer treatment. Novel adjuvant, amphiphilic nanoparticles (NPs) composed of L: -phenylalanine (Phe)-conjugated poly(gamma-glutamic acid) (gamma-PGA-Phe NPs) having excellent capacity for carrying peptides, were found to have the potential for use as a peptide vaccine against tumor models overexpressing artificial antigens, such as ovalbumin (OVA). However, the anti-tumor potential of gamma-PGA-Phe NPs vaccines using much less immunogenic tumor-associated antigen (TAA)-derived peptide needs to be clarified. In this study, we evaluated the effectiveness of immunization with EphA2, recently identified TAA, derived peptide-immobilized gamma-PGA-Phe NPs (Eph-NPs) against mouse liver tumor of MC38 cells (EphA2-positive colon cancer cells). Immunization of normal mice with Eph-NPs resulted in generation of EphA2-specific type-1 CD8+ T cells. Immunization with Eph-NPs tended to provide a degree of anti-MC38 liver tumor protection more than that observed for immunization with the mixture of EphA2-derived peptide and complete Freund's adjuvant (Eph + CFA). Neither Eph-NPs nor Eph + CFA vaccines inhibited tumor growth of BL6, EphA2-negative melanoma cells. Splenocytes isolated from MC38-bearing mice treated with Eph-NPs showed strong and specific cytotoxic activity against MC38 cells. Immunization with Eph + CFA induced liver damage as evidenced by elevation of serum alanine aminotransferase, while Eph-NPs vaccination did not exhibit any toxic damage to the liver. These results demonstrated that immunization with Eph-NPs displayed anti-tumor effects against liver tumor by generating acquired immunity equivalent to the toxic adjuvant CFA, suggesting that safe gamma-PGA-Phe NPs could be applied clinically for the vaccine treatment of liver cancer.
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Japan.
authors: Shinjiro
authors: S
authors: Yamaguchi
authors: Tomohide
authors: T
authors: Tatsumi
authors: Tetsuo
authors: T
authors: Takehara
authors: Akira
authors: A
authors: Sasakawa
authors: Masashi
authors: M
authors: Yamamoto
authors: Keisuke
authors: K
authors: Kohga
authors: Takuya
authors: T
authors: Miyagi
authors: Tatsuya
authors: T
authors: Kanto
authors: Naoki
authors: N
authors: Hiramastu
authors: Takami
authors: T
authors: Akagi
authors: Mitsuru
authors: M
authors: Akashi
authors: Norio
authors: N
authors: Hayashi
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant; D008113:Liver Neoplasms / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D036104:Receptor, EphA2 / Q000276:immunology*; D013501:Surface-Active Agents / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D013501:Surface-Active Agents; D022223:Vaccines, Subunit; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D005620:Freund's Adjuvant; D036104:Receptor, EphA2