The goal of immunotherapy is to overcome the deficits of the host or the tumor itself and activate an effective immune response to the tumor. In the case of virus-associated malignancies, immunotherapeutic strategies can be either prophylactic (prevention of infection or prevention of tumor outgrowth in already infected individuals) or therapeutic (targeting the immune response against viral proteins expressed in tumor cells). In both applications, CTLs are regarded as the most important effector arm of the immune response against tumor or virus-infected cells, and they may be activated in vivo or ex vivo (Fig. 2). In vivo approaches such as vaccination aim to evoke an immune response by administration of an immunogen such as a peptide or DNA directly into patient. In the ex vivo approach, CTLs are activated and expanded in vitro, in a culture environment conducive to CTL growth, and then adoptively transferred into a recipient.
A tumor cell may fail to activate an effective immune response in the host for a number of reasons. First, tumor cells may fail to express an antigen that is perceived as foreign. In virus-associated malignancies, peptides derived from viral proteins can provide the target epitopes for CTLs. Second, tumor cells may fail to provide the costimula-tory signals needed to activate CTLs. Optimal CTL induction can be achieved with professional APCs (e.g., DCs). Third, tumor cells may have mechanisms that inhibit the
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