[Anticancer immunotherapy with perorally effective lentinan]

Lentinan is a beta(1-3) glucan clarified to have a life prolonging effect in non-operable, recurrent gastric cancer patients in combination with chemotherapy. The long lasting issue remaining to be resolved has been the ineffectiveness of Lentinan when administered per-orally. Beta(1-3) glucans possess the particulate size around 100-200 microm in aqueous solution which dampered the absorption through abdominal mucosa. Subsequently the particulate size of Lentinan impaired the immunostimulating potency, to induce reductive form of antigen presenting cells, macrophages and dendritic cells relevant for the polarization of Th1/Th2 balance to Th1. The situation is also the case for the clinical benefit of lentinan to reduce the side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP, known to be a critical dose limiting factor of these agents and to improve quality of life of the patients. Using the modern nano-technology procedures, Mitherapist, containing 15 mg/dl Lentinan, with a particulate size of 0.2 microm able to pass through mucosal barrier was provided. It was found in randomized double blind clinical testing that Mitherapist is effective against allergy by reducing an antigen specific IgE level through polarization to Th1 biased immune response even by per-oral administration. Per oral administration also exhibited the reduced side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP and greatly improved quality of life of the cancer patients. The role of hypoxia in local neoplastic tissues will be also discussed.