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Mouse model exposes a new type of T cell to target melanoma
Date:10/25/2012

October 24, 2012, New York, NY Cancers arise in the body all the time. Most are nipped in the bud by the immune response, not least by its T cells, which detect telltale molecular markersor antigenson cancer cells and destroy them before they grow into tumors. Cancer cells, for their part, evolve constantly to evade such assassination. Those that succeed become full-blown malignancies. Yet, given the right sort of help, the immune system can destroy even these entrenched tumors.

In the October 22nd issue of the Journal of Experimental Medicine, researchers led by Jedd Wolchok, MD, PhD, of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York describe one way in which that might be achieved. The paper relates how the cancer drug cyclophosphamide (CTX) and OX86an antibody that activates a molecule named OX40 on T cellswere combined with a cutting-edge therapy known as adoptive T cell transfer to eradicate advanced melanoma tumors in mice.

Wolchok and his colleagues had previously shown that CTX and OX86 treatment caused the regression of such tumors. Now they wanted to see if adding T cell transfer to the mix would further improve outcomes. T cell transfer is an investigative immunotherapy in which T cells that target tumors are isolated from patients, manipulated, expanded and then transfused back into those patients.

A variety of T cells are of relevance to this approach. One is the CD8+ T cell, which can directly kill diseased and cancerous cells. Another is the CD4+ T cell, whose general role is to orchestrate the immune assault. It comes in several varieties examples are the T helper 1 (Th1) and T helper 2 (Th2)each of which elicits a distinct sort of immune response. And then there is the regulatory T cell, which keeps a lid on the last two responses.

The activation of OX40 on T cells has varying effects. "When OX40 is activated on regulatory T cells in the
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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