The Evaluation of α-Galactosylceramide Incorporated Liposomes as Targeted and Immunostimulatory Carriers of Antigen for Cancer Immunotherapy
Date Issued
2015
Date
2015
Author(s)
Jiang, Ping-Lun
Abstract
Cancer is a terrible disease characterized by abnormal cell growth and metastasis, which is the potential to invade or spread to other parts of the body. Although many clinical therapies are used to kill the cancer cells, these therapies usually cause a variety of side effects and show low survival in some particular type of cancer. Cancer immunotherapy is the use of one person’s immune system to treat or destroy cancer. Over the years, the researchers believe that successful stimulation of the patient’s own immune system are able to eliminate cancer and are able to significantly improve the survival rate of cancer patients without producing serious side effects. Therefore, how to induce effective immune responses to treat various types of cancer has been an extremely important issue. Alpha-Galactosylceramide is a potent vaccine adjuvant in protecting against tumors. In this study, α-GalCer was incorporated into lipid-bilayer of liposome and exposed galactose molecules on the outer surface of liposome. Ovalbumin (OVA) was then encapsulated into α-GalCer incorporated liposomes. We evaluate whether α-GalCer incorporated liposomes could act as an effective DC-targeted mucosal vaccine that could facilitate antigen delivery familiar to galactosylated liposomes we have published. The immunoregulatory effects of α-GalCer incorporated liposomes were also evaluated. The particle sizes of each liposome formulation were controlled to are approximately 1000-1100 nm and OVA encapsulation efficiencies are approximately 30-40%. We demonstrated that α-GalCer incorporated liposomes effectively facilitated antigen uptake by mouse bone-marrow derived dendritic cells (BMDCs) in vitro, led to higher expression of maturation markers, including CD80, CD86 and MHC II, and induced higher production of pro-inflammatory cytokines. In vivo uptake of α-GalCer incorporated liposomes by DCs in nasopharynx-associated lymphoid tissue (NALT) showed the similar results. C57BL/6 mice immunized intranasally with OVA-encapsulated α-GalCer incorporated liposomes produced high levels of OVA-specific IgG antibodies in their serum and secretory-IgA (s-IgA) in nasal wash fluid. Spleen cells from mice receiving α-GalCer incorporated liposomes were re-stimulated with OVA and showed significantly augmented levels of IFN-γ and IL-4, and increase number of IFN-γ producing CD8+ cells. In addition, intranasal administration of α-GalCer incorporated liposomes resulted in complete protection against EG7 tumor challenge in C57BL/6 mice. Taken together, these results indicate that nasal administration of α-GalCer incorporated liposomes mediates the development of an effective immunity against tumors and might be useful for further clinical anti-tumoral applications.
Subjects
Alpha-Galactosylceramide
Targeted liposome
Antigen delivery
Mucosal immunity
Cancer vaccine
SDGs
Type
thesis