Oncotarget

Research Papers:

Immune adjuvant effect of a Toxoplasma gondii profilin-like protein in autologous whole-tumor-cell vaccination in mice

Kyoung-Ho Pyo, You-Won Lee, Sun Min Lim and Eun-Hee Shin _

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Oncotarget. 2016; 7:74107-74119. https://doi.org/10.18632/oncotarget.12316

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Abstract

Kyoung-Ho Pyo1,4, You-Won Lee1, Sun Min Lim2, Eun-Hee Shin1,3

1Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea

2Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Republic of Korea

3Seoul National University Bundang Hospital, Seongnam, Republic of Korea

4Current address: JE-UK Laboratory of Molecular Cancer Therapeutics, Yonsei Cancer Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

Correspondence to:

Eun-Hee Shin, email: [email protected]

Keywords: Toxoplasma gondii, Toll-like receptor, profilin, antitumor, vaccine

Received: July 15, 2016    Accepted: September 21, 2016    Published: September 28, 2016

ABSTRACT

Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR) agonist. In this study, we investigated whether TgPLP has an adjuvant effect on immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice vaccinated with AWV together with recombinant TgPLP protein had smaller CT26 tumors and increased survival. TgPLP treatment strongly increased the production of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12, and XCL1, in bone marrow-derived macrophages (BMMs). In addition, TgPLP increased the phagocytosis of tumor cells by BMMs and promoted immune cell mobility on a tumor-matrigel scaffold. TgPLP triggered immune responses as demonstrated by increased expression of antigen presenting cell markers (MHC class I and II, B7.1, and B7.2) in BMMs and increased IL-12 and IFN-γ expression in mice. Mice vaccinated with AWV and TgPLP had more immune cells (CD4+ and CD8+ T cells, natural killer cells, and macrophages) in the spleen and higher total IgG and IgG2a concentrations in the blood than mice vaccinated with AWV alone. These findings suggest that TgPLP is a TLR-based vaccine adjuvant that enhances antitumor immune responses during vaccination with AWV.


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