Background: Previous accidental findings showed that administration of immunoglobulin G (IgG) in treating autoimmune diseases was able to inhibit cancers that happened to grow in these patients. However, such treatment has not been used to treat cancer patients clinically. The mechanism and optimal dosages of this treatment have not been established. Subsequent animal experiments confirmed this effect, but all previous studies in animal models used human IgG which was heterogeneous to the animal hosts and therefore could adversely interfere with the results.
Materials and methods: We tested different dosages of mouse IgG in treating and preventing three syngeneic cancer types (melanoma, colon cancer, and breast cancer) in three immune potent mouse models. The expression of Ki67, CD34, VEGF, MMPs, and cytokines in tumor tissues were examined with immunohistochemistry or quantitative real-time PCR to evaluate tumor proliferation, vascularization, metastasis, and proinflammatory response in the tumor microenvironment.
Results: We found that low-dose IgG could effectively inhibit cancer progression, regulate tumor vessel normalization, and prolong survival. Administration of IgG before cancer cell inoculation could also prevent the development of cancer. In addition, IgG caused changes in a number of cytokines and skewed macrophage polarization toward M1-like phenotype, characterized by proinflammatory activity and inhibition of proliferation of cancer cells.
Conclusion: Our findings suggest that nonspecific IgG at low dosages could be a promising candidate for cancer prevention and treatment.
Keywords: IVIg; cancer therapy; immunotherapy; macrophages; mouse model.