Chronic lymphocytic leukemia (CLL) cells genetically modified to express B7-1, ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients.

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Chronic lymphocytic leukemia (CLL) cells genetically modified to express B7-1,

ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients.

T Litzinger, A Foon, Helen Sabzevari, Kwong-Yok Tsang,

Schlom, and Palena

Cancer Immunol Immunother, November 14, 2008; .

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National

Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, MSC

1750, Bethesda, MD, 20892, USA.

In chronic lymphocytic leukemia (CLL), malignant B cells and nonmalignant T

cells exhibit dysfunction. We previously demonstrated that infection of CLL

cells with modified vaccinia Ankara (MVA) expressing the costimulatory molecules

B7-1, ICAM-1, and LFA-3 (designated TRICOM) increased expression of these

costimulatory molecules on the surface of CLL cells and thus augmented their

antigen-presenting capability. Here, we evaluate the effect of

MVA-TRICOM-modified CLL cells on T cells. Following incubation with irradiated

MVA-TRICOM-modified CLL cells, allogeneic and autologous CD4(+) and CD8(+) T

cells expressed significantly higher levels of B7-1, ICAM-1, and LFA-3. We show

that this increase was the result of physical acquisition from the

antigen-presenting cells (APCs), and that purified T cells that acquired

costimulatory molecules from MVA-TRICOM-modified CLL cells were able to

stimulate the proliferation of untreated T cells. These results demonstrate for

the first time that T cells from CLL patients can acquire multiple costimulatory

molecules from autologous CLL cells and can then act as APCs themselves. Given

the immunodeficiencies characteristic of CLL, enhancing the antigen-presenting

function of CLL cells and T cells simultaneously could be a distinct advantage

in the effort to elicit antitumor immune responses.

PMID: 19009294