Cure of colon cancer metastasis in rats with the new lipid A OM 174. Apoptosis of tumor cells and immunization of rats.
The antitumoral effect of the new lipid A OM 174 was investigated in a model of colon cancer in rats. Peritoneal carcinomatosis were induced in BDIX rats by intraperitoneal injection of syngeneic PROb cancer cells. The treatment started 2 weeks later, when rats had macroscopic peritoneal nodules. An antitumoral effect was first obtained with OM 174 intraperitoneally injected, then an intravenous treatment was developed. When injected 15 times intravenously, at the dose of 1 mg/kg, 2 days apart, OM 174 induced the complete regression of tumors and hemorrhagic ascitis in 90% of the tumor-bearing rats, whereas all the untreated rats died of their tumors. To our knowledge, this treatment is the most effective ever applied to macroscopic tumors. Furthermore, the treatment induced the immunization of rats since the reinjection of PROb tumor cells in OM 174-cured rats did not cause the formation of new tumors while injection of another syngenic colon tumor cells did. Only in treated rats tumors were infiltrated with lymphocytes, macrophages and fibroblasts. The treatment did not increase necrosis but generated apoptotic areas. OM 174 was not directly toxic for tumor cells, and thus the observed effect involved the host-mediated antitumor reaction. Therefore we hypothesize that OM 174 therapy induces tumor cell apoptosis, stimulates the phagocytosis of apoptotic bodies and then activates immune system by antigen presentation.
Onier
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Laboratoire d'Immunologie et d'Immunothérapie des Cancers de l'Ecole Pratique des Hautes Etudes, INSERM U517, Université de Bourgogne, Faculté de Médecine, Dijon, France.
Hilpert
S
S
Arnould
L
L
Saint-Giorgio
V
V
Davies
J G
JG
Jeannin
J F
JF
Jeannin
J F
JF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008297:Male; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000628:therapy; D051381:Rats; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D008070:Lipopolysaccharides; C400105:defoslimod