Human IgM Antibody Targeting GD2 Suppresses Tumor Growth: A Focused Review

The human IgM monoclonal antibody, MORAb-028, has demonstrated a high affinity for the tumor-associated antigen GD2 and is capable of inducing the destruction of tumor cells through complement-dependent cytotoxicity (CDC). This study aimed to evaluate the in vivo anti-tumor efficacy of MORAb-028 in nude rats using two distinct models, which were designed to circumvent the limitations posed by the rodent poly-Ig-Receptor (PIgR) that typically sequesters human IgM in the liver.

In one model, EL4-luc2 cells, which are known for their high GD2 expression and the inclusion of a bioluminescent reporter gene for tracking, were injected into the peritoneal cavity of the rats. These rats were then administered a single intraperitoneal dose of MORAb-028. The progression of the tumors was monitored using an imaging system, and a significant reduction in tumor growth was observed in the treated group compared to the controls.

In another model, the same cell line was implanted subcutaneously, and MORAb-028 was injected directly into established tumors. This treatment resulted in a significant inhibition of tumor growth and complete eradication of the tumor in approximately 30% of the cases. The volume of the tumors in the treated animals was substantially smaller than that in the control group, with no signs of recurrence observed at the study's conclusion.

The findings suggest that MORAb-028 is an effective agent against GD2-positive tumors in rats and may hold potential for clinical applications in treating human cancers expressing GD2. The study was presented at the 102nd Annual Meeting of the American Association for Cancer Research, with the abstract published in the Cancer Research journal.