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T vs. B: Re-engineered human T cells effectively target and kill cancerous B cells
Date:9/18/2007

In order to get T cells to recognize B cells, Dr. Brentjens and his colleagues created a gene that encodes for a cell-surface protein an artificial T cell receptor called a chimeric antigen receptor -- designed to specifically bind to CD19, a molecule found on the surface of B cells and B cell cancers. Antigen receptors are what allow T cells, in combination with other parts of the immune system, to recognize and attack infected or malignant cells. This chimeric gene, formed from active portions of several immune system-related genes, creates the chimeric antigen receptor protein called 19-28z, which does not require other co-stimulatory signals to fully activate T cells, according to Dr. Brentjens.

Dr. Brentjens and his colleagues used an engineered retrovirus to insert the chimeric antigen receptor gene into T cell DNA. Retroviruses insert DNA derived from their RNA into that of a host cell, which then uses viral vector-encoded genes to make specific proteins. In this case, the researchers infected healthy T cells with modified retroviruses containing the gene that codes for 19-28z. The T cells internal protein-making facilities then produce the chimeric receptor as if it were one of its own natural antigen receptors.

In Clinical Cancer Research, the MSKCC researchers detail the creation of 19-28z, their second generation chimeric antigen receptor, and its effectiveness in stimulating human T cells both in culture and in an animal model of human cancer. They also compared T cells engineered with 19-28z to T cells engineered with a first generation chimeric antigen receptor, lacking the co-stimulatory signal found in 19-28z. Their results showed that the second generation 19-28z receptor was superior to the first generation receptor, and that this T cell therapy works best when administered to mice through multiple weekly injections.

The repeated boosts of new T cells during therapy to improve T cell persistence enhances the effic
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Contact: Greg Lester
lester@aacr.org
267-646-0554
American Association for Cancer Research
Source:Eurekalert

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