Therapeutic effects of a synthetic peptide of C-reactive protein in pre-clinical 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 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.
Barna
B P
BP
Department of Immunopathology, Cleveland Clinic Foundation, One Clinic Center, Ohio 44195.
Eppstein
D A
DA
Thomassen
M J
MJ
Nestor
J J
JJ
Ho
T
T
Medendorp
S V
SV
Deodhar
S D
SD
D000230:Adenocarcinoma / Q000628:therapy; D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000628:therapy; D003110:Colonic Neoplasms / Q000628:therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005354:Fibrosarcoma / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000628:therapy; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D010446:Peptide Fragments / Q000494:pharmacology*; D012045:Regulatory Sequences, Nucleic Acid
C079903:C-reactive protein (164-173); C079904:C-reactive protein (192-201); D004337:Drug Carriers; D010446:Peptide Fragments; D002097:C-Reactive Protein