Uncovering the Hidden Potential of Intravenous Immunoglobulin as an Anticancer Therapy

Abstract

Intravenous immunoglobulin (IVIg) is a safe preparation made from human plasma. The original concept of IVIg as an anticancer drug was built up over the years, after numeral reports were accumulated indicating cancer regressions after IVIg administration. Because IVIg is basically an established remedy for immunodeficiencies and several autoimmune diseases, the association between beneficial effects in cancer patients after IVIg was first seen in patients who had both cancer and autoimmune or immunodeficiency diseases. Interestingly, cancer and autoimmunity share several common features, which together enhance the notion of using IVIg to treat cancer. Several studies tested the broad range of the antimetastatic effects of IVIg. IVIg was found to operate in many different and complex ways, among them (a) induction of interleukin-12 secretion, leading to natural-killer-cell activation; (b) inhibition of matrix metalloproteinase-9 mRNA expression; (c) suppression of tumor cell growth; (d) hindrance of nuclear factor kappaB activation and IkappaB degradation; and (e) G1 cell-cycle arrest. In conclusion, IVIg is a potential anticancer treatment for several reasons: (a) the bidirectional relationship between cancer and autoimmunity; (b) the apparent association between cancer regression and IVIg administration; (c) a variety of anticancer effects of IVIg observed; and (d) IVIg is considered to be a safe preparation with minimal side effects. Obviously, prospective controlled studies that will establish the antitumor effects of IVIg are needed.

Intravenous Immunoglobulin Promotes Antitumor Responses by Modulating Macrophage Polarization

“…The coexistence of autoimmune pathologies and cancer has previously provided evidence that IVIg therapy promotes regression of cancer in patients with chronic lymphatic leukemia, Kaposi's sarcoma, and melanoma (42). Given the importance of the polarization of TAM for tumor progression and dissemination (37), our results establish a sequential link between the IVIg ability to modulate macrophage polarization and its antitumor effect, suggesting that the proinflammatory activities of IVIg might also be therapeutically useful in pathologies (2) or IVIg treated, either with or without clodronate liposome-mediated depletion of macrophages.…”

Attenuation of Colon Carcinoma Tumor Spread by Intravenous Immunoglobulin

“…Although not wishing to be bound by any particular theory, we propose that the IVIg inhibits metastases by one or more of the following mechanisms (reviewed in Ref. 20). First, our previous in vitro studies revealed that IVIg led to significant enhancement of IL‐12 cytokine secretion by mononuclear cells.…”

Humoral immunity, inflammation and cancer

“…Considering the fact that tissues damaged by autoimmune dysfunction and by cancer have similar characteristics (e.g. chronic innate immune cell infiltration, tissue remodeling, angiogenesis, altered cell survival pathways) [48], it seems probable that similar IC effector pathways are involved in pathogenesis of both diseases.…”