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Learning from Viruses: The Necrotic Bodies of Tumor Cells with Intracellular Synthetic dsRNA Induced Strong Anti-tumor Immune Responses

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Abstract

Purpose

Coaxing dead tumor cells to induce specific immune responses is an attractive tumor therapy. However, there continues to be a need for adjuvants that can promote the cross-presentation of the dead tumor cells to induce specific anti-tumor response. Viral dsRNA has multiple mechanisms to promote the cross-presentation of viral antigens in virus-infected cells. We propose to learn from viruses by generating dead tumor cells having synthetic dsRNA delivered inside them to allow the dsRNA to promote the cross-presentation of dead tumor cells.

Materials and Methods

Using synthetic dsRNA, poly(I:C), and the TC-1 cervical cancer model, we evaluated the extent to which the poly(I:C) can promote the necrotic bodies of TC-1 cells to induce specific anti-tumor immune response. The poly(I:C) was either simply mixed with the dead TC-1 cells or pre-loaded inside them.

Results

Immunization of tumor-bearing mice with the necrotic bodies of tumor cells admixed with poly(I:C) significantly inhibited the tumor growth. More importantly, immunization with the necrotic bodies having poly(I:C) pre-loaded inside led to a significantly stronger anti-tumor response than when the necrotic bodies were simply admixed with the poly(I:C), apparently through a CD8+ CTL response-mediated mechanism.

Conclusions

These findings are expected to be clinically relevant for devising improved whole cell-based tumor vaccines.

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Acknowledgements

This work was supported in part by a grant from the Elsa U. Pardee Foundation and an OSU College of Pharmacy Translational Research Grant to Z.C. We would like to thank Malcolm Lowry for discussions.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, 97331, USA

    Zhengrong Cui, Uyen M. Le, Fu Qiu & Dalia S. Shaker

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  1. Zhengrong Cui
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Correspondence to Zhengrong Cui.

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Cui, Z., Le, U.M., Qiu, F. et al. Learning from Viruses: The Necrotic Bodies of Tumor Cells with Intracellular Synthetic dsRNA Induced Strong Anti-tumor Immune Responses. Pharm Res 24, 1645–1652 (2007). https://doi.org/10.1007/s11095-007-9293-5

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