THERAPEUTIC EFFECTS OF A SYNTHETIC PEPTIDE OF C-REACTIVE PROTEIN IN PRECLINICAL TUMOR-MODELS

Previous studies have shown that multilamellar vesicles (MLV) or other carriers containing purified human C-reactive protein (CRP) have therapeutic activity in preclinical tumor models. Here we evaluated the therapeutic effects of MLV containing novel synthetic peptides, derived from the structure of CRP, on the extent of (a) established lung metastases of fibrosarcoma T241 in C57B1/6 mice, (b) survival of C57B1/6 mice bearing established liver metastases of colon carcinoma MCA-38, and (c) primary tumor growth of Renca renal carcinoma in Balb/c mice. In all cases, a single synthetic CRP peptide, RS-83277, demonstrated significant antitumor effects comparable to that seen with intact CRP. Two other synthetic CRP peptides, RS-83287 and RS-83147, showed no therapeutic activity and were comparable to control MLV containing only buffer. None of the peptides contained sequences homologous with that of the phagocyte stimulant, tuftsin. Activity of MLV-encapsulated RS-83277 was dose-dependent, and a comparable dose of the soluble peptide, given either alone or following injection of buffer-MLV, was ineffective. These results demonstrate immunotherapeutic potential for a novel synthetic peptide derived from CRP, and endogenous acute-phase protein.