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Current Topics in Complement II pp 152–167Cite as

The Role of Membrane Complement Regulatory Proteins in Cancer Immunotherapy

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 632))

Abstract

Anti-tumor monoclonal antibody therapy represents one of the earliest targeted therapy in clinical cancer care and has achieved a great clinical promise. Complement activation mediated by anti-tumor mAbs can result in direct tumor lysis or enhancement of antibody-dependent cellular cytotoxicy. Chemotaxis of phagocytic cells by complement activation products C5a is also required for certain cancer immunotherapy such as combined β -glucan with anti-tumor mAb therapy. However, high expression levels of membrane-bound complement regulatory proteins (mCRPs) such as CD46, CD55 and CD59 on tumors significantly limit the anti-tumor mAb therapeutic efficacy. In addition, mCRPs have been shown to directly or indirectly down-regulate adaptive T cell responses. Therefore, it is desirable to combine anti-tumor mAb therapy or tumor vaccines with the blockade of mCRPs. Such strategies so far include the utilization of neutralizing mAbs for mCRPs, small interfering RNAs or anti-sense oligos for mCRPs, and chemotherapeutic drugs or cytokines. In vitro studies have demonstrated the feasibility and efficacy of such methods although concerns have been raised about the for utilization of neutralizing mAbs in vivo due to widespread expression of mCRPs on normal cells and tissues. Strategies have been developed to address these issues and more in vivo studies are needed to further validate these combination approaches.

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Acknowledgements

This work was supported by NIH/NCI RO1 CA86412, the Kentucky Lung Cancer Research Board, the James Graham Brown Cancer Center Pilot Project Program to J.Y. and by the MRC New Investigator Grant 81345 to R.D.

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Authors and Affiliations

  1. Tumor Immunobiology Program of the James Graham Brown Cancer Center, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA

    Jun Yan

  2. Complement Biology Group, Department of Medical Biochemistry and Immunology, chool of Medicine, Cardiff University, UK

    Rossen Donev

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  1. Jun Yan
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  2. Daniel J. Allendorf
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  3. Bing Li
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  4. Ruowan Yan
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  5. Richard Hansen
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  6. Rossen Donev
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Correspondence to Jun Yan .

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    Yan, J., Allendorf, D., Li, B., Yan, R., Hansen, R., Donev, R. (2008). The Role of Membrane Complement Regulatory Proteins in Cancer Immunotherapy. In: Lambris, J. (eds) Current Topics in Complement II. Advances in Experimental Medicine and Biology, vol 632. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78952-1_12

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