Augmentation of virus-specific immunity after hematopoietic stem cell transplantation by adoptive T-cell therapy

Abstract

Adoptive transfer of virus-specific T cells offers the potential for accelerating reconstitution of antigen-specific immunity after allogeneic hematopoietic stem cell transplantation. However, the logistics of producing virus-specific T cells and the risk of inducing graft-versus-host disease has limited their application. We developed a relatively simple system employing cytomegalovirus lysate-pulsed, monocyte-derived dendritic cells as stimulator cells, requiring only a single blood draw from the donor. We treated 16 patients with these T-cell lines, administered after the detection of human cytomegalovirus (HCMV) DNA by polymerase chain reaction. Massive in vivo expansions of HCMV-specific cytotoxic T lymphocytes (3-5 log) were observed within days of adoptive transfer. In eight cases viral titers were decreasing within 5 days and antiviral drug therapy was not required. The T-cell receptor CDR3 lengths of HCMV-specific cytotoxic T lymphocytes expanding in vivo were identical to those of the transferred cells. A low incidence of late CMV reactivation was seen (2/14 assessable patients compared with 45/72 historical controls, p = 0.001) and no significant toxicities were observed. Our findings indicate that application of cell lines generated in relatively short-term in vitro cultures is both feasible and effective in a clinical environment. This simple in vitro methodology should allow widespread application of adoptive transfer of virus-specific T cells.