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Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
Induction of natural killer cell-dependent antitumor immunity by the Autographa californica multiple nuclear
Masayuki Kitajima1, Takayuki Abe, Naoko Miyano-Kurosaki
1Department of Life and Environmental Sciences, Chiba Institute of Technology, Narashino, Chiba, Japan.
Abstract:
Wild-type Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a variety of mammalian cell types in vitro, but does not replicate in these cells. We investigated the effects of AcMNPV in the induction of the immune response and tumor metastasis in mice. After intravenous injection, AcMNPV was taken up by the liver and spleen, and preferentially infected dendritic cells (DCs) and B cells in the spleen; costimulatory molecules CD40, CD80, and CD86 were upregulated in the DCs. The hepatic mononuclear cells (MNCs) in these animals were highly cytotoxic to natural killer (NK)-sensitive YAC-1 and B16 melanoma cells, but not to NK-resistant EL4 cells. Intravenous injection of AcMNPV-induced NK cell proliferation in the liver and spleen, and enhanced antitumor immunity in mice with B16 liver metastases. Furthermore, such treatment increased the survival of C57BL/6, J alpha 281 (-/-), and interferon (IFN)-gamma (-/-) mice that were previously injected with B16 tumor cells. AcMNPV injection did not enhance the survival of NK cell-depleted mice. Moreover, one AcMNPV treatment effectively prolonged survival in a B16 liver metastasis model, and was equivalent to five treatments with recombinant interleukin-12 (IL-12) protein. These findings suggest that AcMNPV efficiently stimulates NK cell-mediated antitumor immunity.
Insights
Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) boosts natural killer (NK) cell activity and antitumor immunity in mice. This viral treatment enhanced survival in tumor metastasis models, suggesting potential therapeutic applications.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects mammalian cells but does not replicate.
- Investigating AcMNPV's impact on immune response and tumor metastasis is crucial.
Purpose of the Study:
- To evaluate the effects of AcMNPV on immune response and tumor metastasis in mice.
- To determine AcMNPV's potential in stimulating antitumor immunity.
Main Methods:
- Intravenous injection of AcMNPV in mice.
- Analysis of immune cell populations (dendritic cells, B cells, NK cells) and their activation markers (CD40, CD80, CD86).
- Assessment of cytotoxic activity against tumor cells and survival rates in B16 liver metastasis models.
Main Results:
- AcMNPV preferentially infected dendritic cells and B cells, upregulating costimulatory molecules.
- Hepatic mononuclear cells exhibited enhanced cytotoxicity against melanoma cells.
- AcMNPV induced NK cell proliferation and enhanced antitumor immunity, significantly increasing survival in tumor-bearing mice.
- The survival benefit was dependent on NK cell activity and comparable to IL-12 treatment.
Conclusions:
- AcMNPV effectively stimulates NK cell-mediated antitumor immunity.
- AcMNPV shows promise as a therapeutic agent for enhancing antitumor responses and combating tumor metastasis.
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