Nonspecific immunoglobulin G is effective in preventing and treating cancer in mice
Authors Xu Q, Zhang Z, Chen Z, Zhang B, Zhao C, Zhang Y, Zhao C, Deng X, Zhou Y, Wu Y, Gu J
Received 20 September 2018
Accepted for publication 24 January 2019
Published 7 March 2019 Volume 2019:11 Pages 2073—2085
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Chien-Feng Li
Qian Xu,1,* Zaiping Zhang,1,* Zhiming Chen,1,* Biying Zhang,1 Chanyuan Zhao,1 Yimin Zhang,1 Conghui Zhao,2 Xiaodong Deng,1 Yao Zhou,1 Yanyun Wu,1 Jiang Gu1–3
1Provincial Key Laboratory of Molecular Pathology and Personalized Medicine, Shantou University Medical College, Shantou 515041, Guangdong, China; 2Department of Pathology, Beijing University Health Science Center, Beijing 100083, China; 3Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, Chengdu 610066, Sichuan, China
*These authors contributed equally to this work
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, macrophages, mouse model, immunotherapy
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