ABSTRACT
In the last decade, immunotherapeutic strategies have gained recognition as viable
alternatives to more conventional therapeutic modalities for the treatment of cancer. The
ability to provide both therapeutic benefit as well as curative potential has moved the
efforts to develop immunotherapeutic approaches into the forefront of cancer research.
In this regard, adoptive T-cell therapy through allogeneic hematopoietic stem cell
transplantation (HSCT) has offered the first evidence that antitumor effects could be
achieved against hematological malignancies (1,2). Theoretically, allogeneic HSCT also
represents one of the few potentially curative treatments for advanced solid tumors,
metabolic and autoimmune disorders, as well as immunodeficiencies. However, donor
T-cell-mediated graft-vs.-host disease (GVHD) continues to be the principal
complication of allogeneic HSCT, along with graft rejection, leukemic relapse, and
opportunistic infections. The depletion of T cells from donor stem cell inocula, while
significantly reducing the development of GVHD, has been clearly associated with
increased incidence of the other risk factors, probably due to slow immunological
reconstitution in the recipients (3-6). Thus, the key to successful allogeneic HSCT lies in
the ability to ameliorate GVHD while still promoting the beneficial T-cell responses of
graft-vs.-leukemia (GVL) effects, enhanced stem cell engraftment, and the capacity to
resist infections.
