Complete regression of Lewis lung carcinoma by cyclophosphamide in combination with immunomodulators

Several types of combination therapy, including OK432, cyclophosphamide (CY), and/or lentinan plus bacterial lipopolysaccharide (LPS), reported to have strong antitumor activity against some tumors, were only slightly effective on Lewis lung carcinoma (LC) in C57BL/6 mice. Combination therapy by intralesional injection of OK432 followed by intraperitoneal administration of CY, lentinan and LPS caused almost complete regression of intradermal solid-type LC. Maximal antitumor activity was observed when lentinan and LPS were administered later than CY. Mice in which LC had regressed due to this combination therapy showed an antitumor delayed hypersensitivity reaction (measured by the footpad test), but they were not resistant to rechallenge with LC. These results provide a new model for combination therapy against weakly immunogenic tumors.