Ex vivo purging of stem cell autografts using cytotoxic cells

Autologous stem cell transplantation (SCT) is the treatment alternative off ered to patients that cannot benefit from allogeneic transplantation due to lack of suitable donor or age limitations. However, the outcome of autolog ous SCT is largely hindered by the high relapse rate. Two major factors can account for relapse after autologous SCT: the persistence of residual mali gnant cells resistant to chemo/radiotherapy left either in the body or in t he autograft. Therefore, the rationale for purging autografts of residual m alignant cells comes from the limitations of conventional high-dose chemo/r adiotherapy in achieving a complete eradication of residual tumor cells in the marrow. To date, different purging modalities have been exploited. Immu nological methods of purging present the advantage of being non-cross-react ive with conventional chemotherapy. These immunologic methods include deple tion using antibody targeting of the malignant cells, ex vivo activation/ge neration of the autologous cytotoxic cells, in particular that of natural k iller/lymphokine-activated killer (NK/LAK) and cytokine-induced killer (CIK ) cells, and ex vivo purging of autografts using cytotoxic cell lines. The generation of ex vivo-expanded and activated autologous cytotoxic cells (CT L or NK) has generated increasing interest for the treatment of different m alignancies. Unfortunately, the isolation and expansion of these cells have proven to be technically difficult. As an alternative, the use of cytotoxi c cell lines as immune effectors has been proposed. The two available human cytotoxic cell lines TALL104 and NK-92 are currently in clinical trials an d a number of studies have suggested their effectiveness as an immunotherap eutic agent including for ex vivo purging of autografts.