Adoptive Immunotherapy of EBV-Associated Malignancies with EBV-Specific Cytotoxic T-Cell Lines

Abstract

The goal of immunotherapy is to overcome the immune response deficits of the host or the immune stimulatory deficits of the tumor and activate an effective tumor-specific immune response. The cytotoxic T-lymphocyte (CTL) arm of the cellular immune response is thought to be the most important defense against tumors and virus-infected cells. CTLs recognize short peptides derived from viral antigens that are carried to the infected cell surface in association with major histocompatibility (MHC) molecules (see Fig. 1). Epstein-Barr virus (EBV)-associated malignancies express a range of antigens against which to target CTLs. For immunotherapy, CTLs may be activated and expanded in vivo or ex vivo. In vivo strategies involve immunization with DNA, tumor vaccines, or antigen- or peptide-loaded dendritic cells. Ex vivo strategies involve exposing T cells to tumor or viral antigens expressed on antigen-presenting cells (APCs) and expanding them in T-cell growth factors in vitro. Although the ex vivo approach may be more costly in the time, effort, and expertise required to grow CTLs for patient infusion, it may be the only option in Fig.1.