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U.S. National Institutes of Health
Cancer Diagnosis Program Cancer Imaging Program Cancer Therapy Evaluation Program Developmental Therapeutics Program Radiation Research Program Translational Research Program Biometric Research Branch Office of Cancer Complementary and Alternative Medicine
Last Updated: 04/25/2012


Ch14.18 Monoclonal Antibody

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.