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Tumor specific phage particles promote tumor regression in a mouse melanoma model

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Abstract

Within cancer research, phage display libraries have been widely used for the identification of tumor targeting peptides and antibodies. Additionally, phages are known to be highly immunogenic; therefore we evaluated the immunotherapeutic potential of tumor specific phages to treat established solid tumors in a mouse model of melanoma. We developed two tumor specific phages, one derived from a peptide phage display library and one Fab expressing phage with known specificity, for the treatment of mice bearing palpable B16-F10 or B16/A2Kb tumors. Therapy in B16-F10 tumor bearing mice with tumor specific phages was superior to treatment with non-tumor specific phages and lead to delayed tumor growth and increased survival. In B16/A2Kb tumor bearing mice, therapy with tumor specific phages resulted in complete tumor regression and long-term survival in 50% of the mice. Histological analysis of tumors undergoing treatment with tumor specific phages revealed that phage administration induced a massive infiltration of polymorphonuclear neutrophils. Furthermore, phages induced secretion of IL-12 (p70) and IFN-γ as measured in mouse splenocyte culture supernatants. These results demonstrate a novel, immunotherapeutic cancer treatment showing that tumor specific phages can promote regression of established tumors by recruitment of inflammatory cells and induction of Th1 cytokines.

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Acknowledgments

Financial support: This work was supported partly by grants from the Cancer Society in Stockholm, the Swedish Cancer Society, Karolinska Institute Funds, the Swedish Research Council (Medical Branch), the EU 6-FP “ALLOSTEM-(LSHB-CT-2004-503319), the EU 6-FP “ENACT-and US Department of Defense Prostate Cancer Research Program (PC030958).

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Authors and Affiliations

  1. Department of Oncology and Pathology, Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, R8:01, Karolinska Institute, 171 76, Stockholm, Sweden

    Fredrik Eriksson, W. David Culp, Lars Egevad & Pavel Pisa

  2. Protein Biochemistry Section, NEI, NIH, 7 Memorial Drive, Bethesda, MD, 20892-0003, USA

    W. David Culp & Donita Garland

  3. Tumor Research Institute, Washington, DC, USA

    Robert Massey

  4. Department of Medicine, Center for Molecular Medicine, L8:01, Karolinska University Hospital, Karolinska Institute, 171 76, Stockholm, Sweden

    Mats A. A. Persson

  5. Cancer Center Karolinska (CCK), R8:01, Karolinska University Hospital, 171 76, Stockholm, Sweden

    Fredrik Eriksson

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  1. Fredrik Eriksson
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Correspondence to Fredrik Eriksson.

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Eriksson, F., Culp, W.D., Massey, R. et al. Tumor specific phage particles promote tumor regression in a mouse melanoma model. Cancer Immunol Immunother 56, 677–687 (2007). https://doi.org/10.1007/s00262-006-0227-6

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  • DOI: https://doi.org/10.1007/s00262-006-0227-6

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