Evaluation of pH-sensitive fusogenic polymer-modified liposomes co-loadedwith antigen and α-galactosylceramide as an anti-tumor vaccine

The Journal of Veterinary Medical Science

Eiji YUBA¹  Shinobu WATARAI²  Seiji OKAZAKI²  Tadashi IWASAKI² 

[1] Department of Applied Chemistry, Graduate School ofEngineering, Osaka Prefecture University, Sakai, Osaka 599-8531,Japan;Division of Veterinary Science, Graduate School of Lifeand Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531,Japan

关键词: cancer immunotherapy;    α-GalCer;    liposome;    pH-sensitive liposome;    tumor vaccine;   

DOI  :  10.1292/jvms.17-0491

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

pH-Sensitive fusogenic polymer-modified (pH-sensitive) liposomes co-loaded with tumormodel antigen, ovalbumin (OVA), and adjuvant, α-galactosylceramide (α-GalCer) werefabricated and administered subcutaneously into mice. The ability of pH-sensitiveliposomes containing OVA and α-GalCer to stimulate cellular and humoral immune responsesin vivo was compared with OVA-encapsulating pH-sensitive liposomes aswell as with OVA alone. After immunization, significant OVA-specific antibodies weredetected in the serum. When sera were analyzed for isotype distribution, antigen-specificIgG1 antibody responses were noted in mice immunized with OVA alone, whereas immunizationwith OVA-containing pH-sensitive liposomes and with pH-sensitive liposomes containing OVAand α-GalCer resulted in the induction of OVA-specific IgG1 and IgG2b antibody responses.Moreover, more substantial production of IFN-γ and IL-4 was demonstrated in spleen cellsfrom mice immunized with pH-sensitive liposomes having OVA and α-GalCer thanOVA-containing pH-sensitive liposomes in vitro. Spleen cells from theimmunized mice showed strong cytotoxic activity against E.G7-OVA tumor cells. In addition,prophylactic vaccination efficacy against tumor formation was evaluated. In all miceimmunized with pH-sensitive liposomes having OVA and α-GalCer, immunization providedsubstantial protection from tumor formation. The therapeutic efficacy of pH-sensitiveliposomes containing OVA and α-GalCer against already established E.G7-OVA tumors was alsoinvestigated. Tumor growth was reduced significantly in all mice treated with pH-sensitiveliposomes having OVA and α-GalCer. The provided evidence on the advantage of antigen andα-GalCer co-encapsulation into pH-sensitive liposomes should be considered in the designof future cancer vaccines for prophylactic and therapeutic purposes.

【 授权许可】

Unknown