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.
Keywords CLL - T cells - Acquisition - Costimulation - Immunotherapy