<p>Nonspecific immunoglobulin G is effective in preventing and treating cancer in mice</p>

Abstract

BackgroundPrevious 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 methodsWe 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.ResultsWe 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.ConclusionOur findings suggest that nonspecific IgG at low dosages could be a promising candidate for cancer prevention and treatment.

Nintedanib and a bi-specific anti-VEGF/Ang2 nanobody selectively prevent brain metastases of lung adenocarcinoma cells

“…Unexpectedly, control IgG treatment showed similar basement membrane normalization effects as Nintedanib did, compared to control gavage treatment. Recently, syngeneic low dose IgG was shown to counteract cancer progression in melanoma, colon cancer and breast cancer mouse models, inhibiting tumor vessel proliferation and prolonging survival [ 36 ]. Anti-tumor effects of unspecific IgG have also been reported using human IgG in animal models [ 36 , 37 ].…”

“…Recently, syngeneic low dose IgG was shown to counteract cancer progression in melanoma, colon cancer and breast cancer mouse models, inhibiting tumor vessel proliferation and prolonging survival [ 36 ]. Anti-tumor effects of unspecific IgG have also been reported using human IgG in animal models [ 36 , 37 ]. In several case reports, cancer patients who received intravenous immunoglobulin (IVIg) therapy e.g.…”

Monoclonal Antibodies Against Human Papillomavirus E6 and E7 Oncoproteins Inhibit Tumor Growth in Experimental Cervical Cancer

“…There is recent clinical and pre-clinical data on using immunoglobulins for cancer therapy. The increasing number of pathologies where intravenous immunoglobulins (IVIg) display a beneficial action illustrates their therapeutic relevance [33], [34]. Possible mechanisms of action include the ability of IVIg to modulate macrophage polarization toward M1-like phenotype, characterized by pro-inflammatory activity and inhibition of proliferation of cancer cells [35].…”

Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade

“…IVIg has been safely employed in the treatment of autoimmune diseases and immunodeficiency. Data from human and animal models have demonstrated that IVIg can inhibit cancer progression as well as prolong survival ( Sobieszczańska et al., 2014 ; Xu et al., 2019 ). A case report of patients with ICI-induced myocarditis showed that treatment with IVIg and statins resulted in rapid recovery from myocarditis without compromising the effectiveness of ICI therapy ( Balanescu et al., 2020 ).…”