CD40-activated B-cell chronic lymphocytic leukemia cells for tumor immunotherapy: Stimulation of allogeneic versus autologous T cells generates different types of effector cells

Although spontaneous remissions may rarely occur in B-cell chronic lymphocy tic leukemia (B-CLL), T cells do generally not develop a clinically signifi cant response against B-CLL cells. Because this T-cell energy against B-CLL cells may be caused by the inability of B-CLL cells to present tumor-antig ens efficiently, we examined the possibility of upregulating critical costi mulatory (B7-1 and B7-2) and adhesion molecules (ICAM-1 and LFA-3) on B-CLL cells to improve antigen presentation. The stimulation of B-CLL cells via CD40 by culture on CD40L expressing feeder cells induced a strong upregulat ion of costimulatory and adhesion molecules and turned the B-CLL cells into efficient antigen-presenting cells (APCs). CD40-activated B-CLL (CD40-CLL) cells stimulated the proliferation of both CD4(+) and CD8(+) T cells. inte restingly, stimulation of allogeneic versus autologous T cells resulted in the expansion of different effector populations. Allogeneic CD40-CLL cells allowed for the expansion of specific CD8(+) cytolytic T cells (CTL). In ma rked contrast, autologous CD40-CLL cells did not induce a relevant CTL resp onse, but rather stimulated a CD4+, Th1-like T-cell population that express ed high levels of CD40L and released interferon-gamma in response to stimul ation by CD40-CLL cells. Together,these results support the view that CD40 activation of B-CLL cells might reverse T-cell anergy against the neoplasti c cell clone, although the character of the immune response depends on the major histocompatibility complex (MHC) background on which the CLL or tumor antigens are presented. These findings may have important implications for the design of cellular immunotherapies for B-CLL. (C) 1999 by The American Society of Hematology.