Currently the highest priority project for DTP/BRB /BDP, Ch14.18 is an anti- GD2+ antibody. GD2 is a surface antigen on neuroblastoma, osteoarcoma, glioblstoma, melanoma, and small cell lung cancer. GD2 is also found on peripheral pain fibers. A family of antibodies against GD2+ was generated in the 1980s in the R. Reisfeld (Scripps Institute) laboratory. Chimerization was performed in collaboration with S. Gillies at Damon/Abbott/Repligen Corp. Two versions, mu14.G2a and ch14.18 mediate antibody-dependent cell-mediated cytotoxicity well with natural killer and granulocyte effector cells.
Phase 1 and 2 studies explored use of these agents singly and in combination, demonstrating modest activity in neuroblastoma as a single agent or in combination with IL-2 or GM-CSF, but with pain as a significant side effect. In 2009, an interim analysis of a randomized controlled phase 3 trial showing a roughly 20 percent increase in event-free survival at 2 years. In discussions with FDA, the control arm was closed and the phase 3 study continued to provide treatment access pending transfer of the product to a commercial entity. A safety trial was opened in the five most active Children’s Oncology Group sites to accumulate additional biologics license application filing.
NCI advertised a cooperative research and development agreement (CRADA) and selected a collaborator. Work is underway on process development for large-scale production. Meanwhile, DTP/BRB/BDP continues to manufacture the entire national supply of antibody, until the collaborator has satisfactorily established and qualified its large-scale commercial process. Extramural investigators continue to explore additional indications for this agent.