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Functional characteristics of antitumor T cells change w increasing time after therapeutic transfer
Date:3/21/2013

PHILADELPHIA Scientists have characterized how the functionality of genetically engineered T cells administered therapeutically to patients with melanoma changed over time. The data, which are published in Cancer Discovery, a journal of the American Association for Cancer Research, highlight the need for new strategies to sustain antitumor T cell functionality to increase the effectiveness of this immunotherapeutic approach.

Early clinical research has indicated that cell-based immunotherapies for cancer, in particular melanoma, have potential because patients treated with antitumor T cells frequently have an initial tumor response; however, those responses are often transient.

"The cell-based immunotherapy we utilized was that of genetically engineered T cells," said James R. Heath, Ph.D., Elizabeth W. Gilloon Professor of Chemistry at the California Institute of Technology in Pasadena, Calif. "This approach is the most widely applicable way to generate large numbers of highly functional antitumor T cells."

Different T cell functions are associated with distinct proteins. Heath and colleagues took a closer look at how genetically engineered T cells functioned or failed after being transferred into patients. To do this, they used a recently developed, multiplexed technology that gave them a high-resolution view of which function-associated proteins individual cells expressed.

The researchers analyzed T cells isolated from blood samples taken from three patients with melanoma at several time points after treatment with genetically engineered antimelanoma T cells. Each of the patients from whom samples were taken had exhibited a different level of response to the immunotherapy.

The most highly functioning genetically engineered antimelanoma T cells made up about 10 percent of the total population of transferred T cells.

"However, they dominated the immune response," Heath said. "In other words, 10 p
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Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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