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Combination therapy with a synthetic peptide of C-reactive protein and interleukin 2: augmented survival and eradication of pulmonary metastases

  • Original Articles
  • Immunotherapy, C-Reactive Protein, Liposomes, Interleukin-2, Synthetic Peptide
  • Published:
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Abstract

A synthetic peptide (RS-83277) derived from the structure of human C-reactive protein (CRP) was previously shown to have antitumor activity in three different murine tumor models when administered in multilamellar vesicles (MLV). The therapeutic effects were comparable to those seen with MLV-encapsulated native CRP. The present study evaluated the therapeutic and immunomodulatory effects of administering CRP peptide RS-83277 MLV simultaneously with low-dose recombinant interleukin-2 (IL-2) to C57B1/6 mice bearing established pulmonary metastases of fibrosarcoma T241. Results demonstrated that the capacity of RS-83277 MLV to inhibit tumor metastases and prolong survival was significantly augmented by combination with 10 000 U/day IL-2 i.p. Treated animals showed no evidence of toxicity. By immunohistochemistry, increased Thy 1.2+ cells were detectable in lungs of RS-83277 MLV/IL-2-treated animals compared to those receiving RS-83277 MLV alone. Circulating tumor necrosis factor α (TNF) and interferon (IFN) were not detectable in animals receiving RS-83277 MLV alone, but TNF was significantly elevated in animals receiving IL-2. In the presence of combination therapy, however, circulating TNF was not detectable. Results suggest that the combination of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a therapeutic advantage over either agent alone.

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Authors and Affiliations

  1. Division of Pathology and Laboratory Medicine, The Cleveland Clinic Foundation, 41195, Cleveland, OH, USA

    Barbara P. Barna, Raymond R. Tubbs, Theresa Chiang, Ping Zhou, Belinda Yen-Lieberman, Sugatha Singh-Burgess & Sharad D. Deodhar

  2. Division of Medicine, The Cleveland Clinic Foundation, 44195, Cleveland, OH, USA

    Mary Jane Thomassen & Mary Maier

  3. The Research Institute, The Cleveland Clinic Foundation, 44195, Cleveland, OH, USA

    Mary Jane Thomassen & Mary Maier

Authors
  1. Barbara P. Barna
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  2. Mary Jane Thomassen
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  3. Mary Maier
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  4. Sharon V. Medendorp
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  5. Raymond R. Tubbs
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  6. Theresa Chiang
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  7. Ping Zhou
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  8. Belinda Yen-Lieberman
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  9. Sugatha Singh-Burgess
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  10. Sharad D. Deodhar
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Additional information

This work was supported in part by grant CA49950 from the National Cancer Institute (B.P.B.), and grant 43618 from the National American Cancer Society (S.D.D.)

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Barna, B.P., Thomassen, M.J., Maier, M. et al. Combination therapy with a synthetic peptide of C-reactive protein and interleukin 2: augmented survival and eradication of pulmonary metastases. Cancer Immunol Immunother 38, 38–42 (1994). https://doi.org/10.1007/BF01517168

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  • DOI: https://doi.org/10.1007/BF01517168

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