Significance of Endogenous Augmentation of Antiganglioside IgM in Cancer Patients

Abstract

Gangliosides expressed by solid malignancies are shed into the circulation at a rate that varies with tumor stage, burden, and progression. Gangliosides have an immunosuppressive effect; thus an increase in the total ganglioside (TG) serum level may coincide with tumor progression. However, circulating gangliosides also may induce an endogenous IgM response. Unlike conventional pentameric IgM antibodies against peptide antigens, antiganglioside IgM antibodies can be polymeric and may not have a J-chain. Because these antibodies can remove shed gangliosides from the tumor microenvironment and the circulation, therapy that actively or passively augments serum levels of IgM against tumor-derived immunosuppressive gangliosides might restore immunocompetence and thereby slow tumor progression. The success of this approach, in passive and active specific therapy of cancer patients, requires analysis of biopsy tissue or sera of therapy recipients to confirm the presence of target gangliosides, such as GM2 or GD3. A patient's response to active or passive immunotherapy against a specific ganglioside target(s) can be monitored by serial assessment of serum specimens for TG level and antiganglioside IgM titer(s). This tailored approach to immunotherapy could be incorporated in postoperative adjuvant protocols.