COMBINATION THERAPY WITH A SYNTHETIC PEPTIDE OF C-REACTIVE PROTEIN AND INTERLEUKIN-2 - AUGMENTED SURVIVAL AND ERADICATION OF PULMONARY METASTASES

A synthetic peptide (RS-83277) derived from the structure of human C-r eactive protein (CRP) was previously shown to have antitumor activity in three different murine tumor models when administered in multilamel lar vesicles (MLV). The therapeutic effects were comparable to those s een 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 (I L-2) to C57B1/6 mice bearing established pulmonary metastases of fibro sarcoma T241. Results demonstrated that the capacity of RS-83277 MLV t o inhibit tumor metastases and prolong survival was significantly augm ented by combination with 10000 U/day IL-2 i.p. Treated animals showed no evidence of toxicity. By immunohistochemistry, increased Thy1.2+ c ells were detectable in lungs of RS-83277 MLV/IL-2-treated animals com pared to those receiving RS-83277 MLV alone. Circulating tumor necrosi s factor alpha (TNF) and interferon (IFN) were not detectable in anima ls receiving RS-83277 MLV alone, but TNF was significantly elevated in animals receiving IL-2. In the presence of combination therapy, howev er, circulating TNF was not detectable. Results suggest that the combi nation of synthetic CRP peptide RS-83277 MLV and low-dose IL-2 offers a therapeutic advantage over either agent alone.