Targeted Immunotherapy Kills Cancer in Mice

Their work appeared in the February 10, 2003, online issue of Nature Medicine.

The researchers genetically engineered an antigen receptor, introduced it into cultured human T cells, and then infused the T cells in mice that bear widespread tumor cells. The modified T cells recognized the targeted antigen present on the tumor cells and eradicated the cancer. Earlier experiments showed that genetically modified human T cells could kill tumor cells in vitro, but the cells could not successfully carry out other immunologic responses such as maintaining cell division and would die prematurely when infused into the body of a mouse.

The investigators, from Memorial Sloan-Kettering Cancer Center (MSKCC, New York, NY, USA; www.mskcc.org), genetically instructed the T cells to target cells that express CD19, a protein found on the surface of normal and cancerous B cells. B cell cancers include leukemias and most lymphomas. Using molecular imaging, the researchers were able to show that patients with advanced chronic lymphocytic leukemia could be targeted in this manner to efficiently kill their own tumor cells in vitro.

"Our findings represent a step forward in the field of adoptive T cell therapy,” said senior author Michael Sedelain, M.D., Ph.D., head of the Gene Transfer and Gene Expression Laboratory at MSKCC. "Our studies aim to better understand the biologic needs of T cells that are targeted to tumors and may potentially be applied to a variety of cancer in the foreseeable future.”




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