Inhibition of liver metastases in murine colon adenocarcinoma by liposomes containing human C-reactive protein or crude lymphokine

Summary Previous studies from our laboratory have shown that liposomes containing LYNK or CRP inhibit lung metastases in mice bearing the malignant fibrosarcoma, T241. We have now extended these observations to the murine colon adenocarcinoma (MCA-38), which metastasizes to the liver. MCA-38 tumor cells (1×10⁶) were implanted in the wall of the cecum by orthotopic transplantation. Three-hundred twenty-six mice bearing such tumors were divided into four treatment groups as follows: (1) no treatment (2) liposomes containing control medium (3) liposomes containing LYNK, and (4) liposomes containing CRP. Treatment was started from day 2, day 18, or 34 after tumor implantation and it was administered on 3 days per week. Each treatment, given parenterally, consisted of 4 mol liposomes (PS-PC, 1:1) containing the appropriate agents. Mice receiving liposomes containing LYNK or CRP had significantly fewer and smaller liver metastases (25%–28%), than those in the two control groups (53%–54%). Also, a significantly better survival was noted in the two treated groups than in the two control groups. The most likely mechanism of tumor inhibition appears to be through macrophage activation. In the Winn tumor neutralization test, peritoneal macrophages harvested from normal mice 24 h after a single injection of liposomes (2.5 mol) containing LYNK or CRP markedly inhibited tumor growth when a mixture of effector-target cells (40:1) was injected in the footpad. These studies further confirm the suggested role of CRP as an immunomodulator or biological response modifier in yet another tumor system. Abbreviations used: LYNK, crude lymphokines; CRP, C-reactive protein; PC, phosphatidylcholine; PS, phosphatidylserine; PEC, peritoneal exudate cells; HBSS, Hank's Balanced Salt Solution; RPMI, Roswell Park Memorial Institute Con A, Concanavalin A; IgG, human gamma globulin; DMH, dimethylhydrazine