Makoto Sugaya

Antitumor effect induced by the expression of granulocyte macrophage-colony stimulating factor gene in murine colon carcinoma cells

Murine colon carcinoma cells which secrete several kinds of cytokine after retroviral transduction with corresponding genes, were examined for their antitumor effects in syngeneic mice. The mice inoculated with granulocyte macrophage-colony stimulating factor (GM-CSF) producer cells showed not only prolonged survival but also reduced tumorigenicity. The antitumor effect caused by the expression of interleukin-4 was less than that of GM-CSF, and interleukin-6 producer cells did not show any effects on the survival of the host animals. Histological examination of the GM-CSF-producing tumor revealed predominant infiltration of neutrophils and necrotic change of the tumor. The present study indicates the feasibility of cancer gene therapy with the expression of GM-CSF gene in tumor cells.

Antitumor effect of murine colon carcinoma cells retrovirally transduced with interleukin-4 and granulocyte macrophage-colony stimulating factor genes.

We have investigated the antitumor effect of murine colon carcinoma cells developed to produce cytokines. Retrovirally transduced cells were inoculated into syngeneic mice, and their survivals were examined. Inoculation of interleukin-4 (IL-4)- or granulocyte macrophage-colony stimulating factor (GM-CSF)-producing cells alone did not affect the survival of the mice. In the tumors derived from an admixture of IL-4 and GM-CSF producers, however, regression developed spontaneously, and prolonged survival of the challenged mice was consequently observed. Histological examination revealed predominant infiltration of neutrophils around the tumor of a mixed population of IL-4 and GM-CSF producers.

Inhibition of peritoneal dissemination of colon carcinoma in syngeneic mice immunized with interleukin-2-producing cells

We have examined the antitumor effect of murine colon carcinoma cells engineered to produce human interleukin-2 (IL-2) in syngeneic mice. Subcutaneous inoculation of retrovirally-transduced cells with IL-2 gene formed small tumors, but they became regressed spontaneously. Consequently, the inoculated mice showed prolonged survival. Histological examination of the tumors derived from IL-2-producers revealed predominant infiltration of macrophages around tumor necrotic masses. Thus, inoculation of IL-2-producing cells could protect the mice from subsequent subcutaneous or intraperitoneal challenges with wild-type cells, suggesting the induction of acquired immunity due to the effect of tumor vaccination.