Barna B P, Eppstein D A, Thomassen M J, Nestor J J, Ho T, Medendorp S V, Deodhar S D
Department of Immunopathology, Cleveland Clinic Foundation, One Clinic Center, Ohio 44195.
Cancer Immunol Immunother. 1993;36(3):171-6. doi: 10.1007/BF01741088.
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 C57Bl/6 mice, (b) survival of C57Bl/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.
先前的研究表明,多层囊泡(MLV)或其他含有纯化人C反应蛋白(CRP)的载体在临床前肿瘤模型中具有治疗活性。在此,我们评估了含有源自CRP结构的新型合成肽的MLV对以下方面的治疗效果:(a)C57Bl/6小鼠中已建立的纤维肉瘤T241肺转移程度;(b)患有已建立的结肠癌MCA-38肝转移的C57Bl/6小鼠的存活率;(c)Balb/c小鼠中Renca肾癌的原发性肿瘤生长。在所有情况下,单一合成CRP肽RS-83277表现出与完整CRP相当的显著抗肿瘤作用。另外两种合成CRP肽RS-83287和RS-83147未显示出治疗活性,且与仅含缓冲液的对照MLV相当。这些肽均不包含与吞噬细胞刺激剂促吞噬素序列同源的序列。MLV包裹的RS-83277的活性是剂量依赖性的,单独给予或在注射缓冲液-MLV后给予相当剂量的可溶性肽均无效。这些结果证明了源自CRP(一种内源性急性期蛋白)的新型合成肽的免疫治疗潜力。