Control of metastatic cancer remains one of the most important goals of cancer therapy. Human cancers frequently metastasize to the lung and many are refractory to conventional modes of chemotherapy. We reported previously that native human C-Reactive Protein (CRP) (a nontoxic endogenous acute phase plasma protein) reduced metastases and prolonged survival of tumor-bearing mice in three different models of established tumor metastasis: fibrosarcoma T241, B16 melanoma, and MCA 38 colon carcinoma. In vitro, CRP enhanced tumoricidal activity of murine and human macrophages. More recently, we have observed that a synthetic CRP peptide can mimic these effects of native CRP and that a combination of synthetic CRP peptide with Interleukin 2 (IL2) has a greater anti-metastatic effect than either agent alone. These data suggest that synthetic CRP peptide represents a novel biological response modifier with anti-metastatic and macrophage activating properties, and the potential to enhance existing cytokine therapy. We propose to evaluate the therapeutic effects of synthetic CRP-peptide alone and in combination with IL2 against established pulmonary metastases of murine fibrosarcoma T241, a malignant, spontaneously metastasizing tumor. Further, we propose to identify and characterize immunologic mechanisms of pulmonary tumor destruction evoked by such therapy.
Our specific aims are to: (1) Establish conditions for obtaining the optimal therapeutic effects of synthetic CRP peptides as a single treatment and in combination with IL2; (2) Evaluate the nature and kinetics of pulmonary immunopathologic changes occurring in situ after treatment with synthetic CRP peptide alone and with IL2, including the characterization of inflammatory leukocytes or mediators; and (3) Using in vitro techniques, characterize the pulmonary immune cells and/or soluble factors responsible for anti-tumor activity and the kinetics of such activity. These studies will enable us to evaluate the potential of synthetic CRP peptide alone and in combination with Interleukin 2 for the treatment of human metastatic cancer.

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National Cancer Institute (NCI)
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Experimental Therapeutics Subcommittee 1 (ET)
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Cleveland Clinic Lerner
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Barna, B P; Thomassen, M J; Zhou, P et al. (1996) Activation of alveolar macrophage TNF and MCP-1 expression in vivo by a synthetic peptide of C-reactive protein. J Leukoc Biol 59:397-402
Zhou, P; Thomassen, M J; Pettay, J et al. (1995) Human monocytes produce monocyte chemoattractant protein 1 (MCP-1) in response to a synthetic peptide derived from C-reactive protein. Clin Immunol Immunopathol 74:84-8
Barna, B P; Thomassen, M J; Maier, M et al. (1994) 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
Barna, B P; Pettay, J; Barnett, G H et al. (1994) Regulation of monocyte chemoattractant protein-1 expression in adult human non-neoplastic astrocytes is sensitive to tumor necrosis factor (TNF) or antibody to the 55-kDa TNF receptor. J Neuroimmunol 50:101-7
Barna, B P; Barnett, G H; Jacobs, B S et al. (1993) Divergent responses of human astrocytoma and non-neoplastic astrocytes to tumor necrosis factor alpha involve the 55 kDa tumor necrosis factor receptor. J Neuroimmunol 43:185-90
Thomassen, M J; Meeker, D P; Deodhar, S D et al. (1993) Activation of human monocytes and alveolar macrophages by a synthetic peptide of C-reactive protein. J Immunother Emphasis Tumor Immunol 13:1-6
Barna, B P; Eppstein, D A; Thomassen, M J et al. (1993) Therapeutic effects of a synthetic peptide of C-reactive protein in pre-clinical tumor models. Cancer Immunol Immunother 36:171-6
Barna, B P; Rogers, L R; Thomassen, M J et al. (1991) Monocyte tumoricidal activity and tumor necrosis factor production in patients with malignant brain tumors. Cancer Immunol Immunother 33:314-8
Estes, M L; Ransohoff, R M; McMahon, J T et al. (1990) Characterization of adult human astrocytes derived from explant culture. J Neurosci Res 27:697-705
Barna, B P; Estes, M L; Jacobs, B S et al. (1990) Human astrocytes proliferate in response to tumor necrosis factor alpha. J Neuroimmunol 30:239-43