The artificial antigen-presenting cells (AAPCs) described in this review were generated to facilitate the production of virus-specific T-cells for the treatment of infections in patients after bone marrow transplant. These AAPCs consist of murine 3T3 cells genetically modified to express critical human molecules needed for T-cell stimulation, such as the co-stimulatory molecules B7. 1, ICAM-1, and LFA-3 and one of a series of 6 common HLA class I alleles. When T-cells were sensitized against cytomegalovirus (CMV) using AAPCs that express a shared HLA allele or using autologous antigen-presenting cells (APCs) loaded with the CMVpp65 antigen, they were activated and expanded to become HLA-restricted CMVpp65-specific T-cells. These T-cells demonstrated functional activity in vitro against CMV by producing IFNγ and inducing CMVpp65-specific cytotoxicity. T-cells sensitized with AAPCs recognized antigenic epitopes presented by each HLA allele known to be immunogenic in Man. Sensitization with AAPCs also permitted expansion of IFNγ+ cytotoxic T-cells against subdominant epitopes that were not effectively recognized by T-cells sensitized with autologous APCs. This panel of AAPCs provides a source of immediately accessible, standardizable, and replenishable" off the shelf" cellular reagents with the potential to make adoptive immunotherapy widely available for the treatment of lethal infections, cancer, and autoimmune diseases.

Therapeutic infusion of T-cells cultured and activated in vitro under specific conditions that empower them to attack and kill virally infected cells or cancer cells is known as adoptive immunotherapy. This type of immune cellular therapy has emerged as an effective approach for the prevention and/or treatment of potentially lethal infections caused by cytomegalovirus (CMV) and Epstein-Barr virus (EBV) that often affect patients during their prolonged immuno-suppressed state after allogeneic hematopoietic stem cell (HSCT) or organ transplants (Walter et al., 1995; Rooney et al., 1998; Einsele et al., 2002; Haque et al., 2002; O’Reilly et al., 2007). Clinical trials using adoptive transfer of T-cells from cancer patients that are activated and expanded ex vivo have also demonstrated that tumor specific T-cells expanded in vitro from the blood of cancer bearing hosts possess anti-cancer activity as shown by regression of metastatic tumors after infusion of the expanded T-cells (Dudley et al., 2002; Hunder et al., 2008). Currently, clinical studies of adoptive transfer of T-cells directed against specific alloantigens (Rooney et al., 1998) or oncofetal proteins differentially expressed by host tumors are also being explored (Bonnet et al., 1999; Marijt et al., 2003; Kloosterboer et al., 2004).