Vaccination with OVA-bound nanoparticles encapsulating IL-7 inhibits the growth of OVA-expressing E.G7 tumor cells in vivo.
Immunotherapy has gained special attention due to its specific effects on tumor cells and systemic action to block metastasis. We recently demonstrated that ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA‑NPs) can manipulate humoral immune responses. In the present study, we aimed to ascertain whether vaccination with OVA-NPs entrapping IL-7 (OVA-NPs-IL-7) are able to induce antitumor immune responses in vivo. Pretreatment with a subcutaneous inoculation of OVA-NPs delayed the growth of thymic lymphoma cells expressing a model tumor antigen OVA (E.G7-OVA), and OVA-NPs-IL-7 substantially blocked the growth of E.G7-OVA tumor cells, although NPs-IL-7 alone had a meager effect, as assessed by the mean tumor size and the percentage of tumor-free mice. However, pretreatment with OVA-NPs-IL-7 failed to reduce the growth of parental thymic tumor cells, suggesting that the antitumor effect was antigen-specific. A tetramer assay revealed that vaccination with OVA-NPs-IL-7 tended to enhance the proportion of cytotoxic T cells (CTLs) specific for OVA. When the tumor-free mice inoculated with OVA-NPs-IL-7 plus EG.7 cells were rechallenged with E.G7-OVA cells, they demonstrated reduced growth compared with that in the control mice. Thus, a single subcutaneous injection of OVA-NPs-IL-7 into mice induced tumor-specific and also memory-like immune responses, resulting in regression of tumor cells. Antigens on NPs entrapping IL-7 would be a promising carrier to develop and enhance immune responses, including humoral and cellular immunity as well as a method of drug delivery to a specific target of interest.
Department of Immunology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan.
Hiroko
H
Toyota
Department of Immunology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan.
Noriko
N
Yanase
Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Shinjuku‑ku, Tokyo 160‑8402, Japan.
Takayuki
T
Yoshimoto
NanoCarrier Co. Ltd., Kashiwa-shi, Chiba 277-0871, Japan.
Mitsunori
M
Harada
NanoCarrier Co. Ltd., Kashiwa-shi, Chiba 277-0871, Japan.
Yasuki
Y
Kato
Department of Immunology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan.
Junichiro
J
Mizuguchi
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D005260:Female; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000008:administration & dosage*; D008810:Mice, Inbred C57BL; D053769:Nanocapsules / Q000008:administration & dosage*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D013945:Thymoma / Q000276:immunology / Q000628:therapy*; D014611:Vaccination; D023041:Xenograft Model Antitumor Assays
D015851:Interleukin-7; D053769:Nanocapsules; D010047:Ovalbumin