Mechanisms of the antitumoral effect of lipid A.
Bacterial lipopolysaccharide (LPS) and its active component, lipid A, have been used either alone or as adjuvant in therapeutic anticancer vaccines. Lipid A induces various transcription factors via intracellular signaling cascades initiated by their receptor CD14-TLR4. These events lead to the synthesis of cytokines, which either have direct cytotoxic effect or stimulate the immune system. Their antitumoral effect has been demonstrated in animal models as well as clinical trials. Studies in animal models showed that their antitumoral effect relies mostly on the generation of an effective immune response. In humans, the antitumoral effect was correlated with an antibody response and cell-mediated cytotoxicity. So far, some encouraging results have been achieved in phase I and II clinical trials with regards to response and stabilization of the disease, but an expansion of the studies and trials is needed to find the best conditions for their clinical application.
Reisser
Danièle
D
Cancer Immunotherapy Research Laboratory, Ecole Pratique des Hautes Etudes, INSERM U517, Faculty of Medicine, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France. reisserd@u-bourgogne.fr
Pance
Alena
A
Jeannin
Jean-François
JF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D008050:Lipid A / Q000494:pharmacology* / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000188:drug therapy
D000970:Antineoplastic Agents; D008050:Lipid A