Improving outcomes of cancer treatment in children greatly depends on the development of new targeted therapies with acceptable short-term and long-term toxicity. Researchers at St. Jude Children’s Research Hospital, an internationally recognized pioneering research and treatment center for of children with cancer and other life-threatening diseases, have received a patent from the United States Patent and Trademark Office for the invention of compositions for genetically modifying human immune cells designed to destroy some of the most common forms of cancer in children and adults.

The newly patented technology represents a potentially potent new therapeutic weapon against such diseases as B-cell acute lymphoblastic leukemia (ALL), B-cell chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (NHL). Each year approximately 71,650 people in the United States are diagnosed with these diseases.

Commenting on receiving the patent, James R. Downing, M.D., St. Jude scientific director, noted “This groundbreaking invention enables human immune cells to recognize and attack certain cells that cause leukemia and lymphoma, cancers of the blood and lymphatic tissue.”

Targeted therapeutics
The new technology is a new form of targeted immunotherapy that merges the targeting specificity of monoclonal antibodies with the cytotoxicity of cytotoxic T cells. In pediatric oncology, CD19 and GD2 are very interesting antigens that have already been identified for targeting pre-B acute lymphoblastic leukemia and neuroblastoma. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of childhood cancer.

Chimeric antigen receptor
The invention involves genetically modifying human immune cells to enable them to manufacture a large protein molecule called a “chimeric antigen receptor” (CAR). The protein molecule is “chimeric” in that it is made from parts that do not exist together in the same molecule in nature. It is a “receptor” because a portion of it extends outside the surface of the immune cell and can receive signals from external “antigens.” An antigen is a substance capable of stimulating an immune response in the human body. The CAR invented by St. Jude fits and latches onto “CD19” antigens prevalent on the B cells that cause ALL, CLL and NHL. It then stimulates the human immune cell to attack and kill the B cells.

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“This exciting invention provides a new and promising treatment option for children and adults with these life-threatening diseases and sets the stage for treating other forms of cancer with cellular immunotherapy,” Downing said.

Available for license
The research that led to this patent was supported in part by a grant (CA 58297) from the National Institutes of Health. Today’s patent is part of St. Jude’s intellectual property portfolio that includes more than 100 issued United States patents. To guarantee widespread use St. Jude will make the technology available for license.

For more information:
Lee DW, Barrett DM, Mackall C, Orentas R, Grupp SAThe future is now: chimeric antigen receptors as new targeted therapies for childhood cancer. Clin Cancer Res.2012 May 15;18(10):2780-90. doi: 10.1158/1078-0432.CCR-11-1920.

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