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

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 C57Bl/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 alpha (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.

The Effect of Synthetic C-Reactive Protein on the In Vitro Immune Response of Human PBMCs Stimulated with Bacterial Reagents

“…The molecular weight is 1.3 k Da, which is about 100th of that of native CRP. The synthetic CRP has been reported to have a biological activity which is similar to that of native CRP [3, 4]. We demonstrated that synthetic CRP generally suppressed the production of the proinflammatory cytokines, TNF, and IL-12, from human macrophages, whereas it did not affect the IFN-γ production from NK cells and T cells.…”

“…Several reports suggested that CRP as well as functional CRP peptides have positive and regulatory effect on the innate immunity against infections and tumors [3, 4], however, the role of CRP on innate immunity has not been fully elucidated. We have recently reported that pretreatment with synthetic CRP prevents mice from developing either lethal endotoxemia or E .…”

C-Reactive Protein and Cancer: Interpreting the Differential Bioactivities of Its Pentameric and Monomeric, Modified Isoforms

“…Deodhar et al ( 29 , 37 ) and Barna et al ( 54 ) reported anti-cancer CRP reagents were effective at preventing metastases and death. The studies by Kresl et al corroborate these findings but extend the understanding to emphasize that the conformation of CRP is a critical factor in eliciting the anti-metastatic effect.…”