Adoptive Transfer of Polyclonal, EBV-Specific Cytotoxic T-Cell Lines for the Prevention and Treatment of EBV-Associated Malignancies

Abstract

There is increasing: interest in using adoptive transfer ofantigen-specific cytotoxic T lymphocytes (CTL) for the treatment ofcancer. The challenges facing this strategy include identification oftumor antigens against which to target CTLs, the development of methodsto activate and expand tumor-specific CTLs in vitro, and ensuring the invivo survival and function of the CTLs in the face of multipleantiimmune response strategies employed by viruses and tumors.Epstein-Barr virus (EBV) provides ideal model systems in which to testthe safety and efficacy of infusions of virus-specific CTLs for thetreatment of tumors with and without immune evasion strategies.EBV-transformed B-cell lines (LCLs) are excellent antigen-presentingcells (APCs) that express nine virus-encoded proteins and can be used tostimulate and expand EBV-specific CTL lines from most donors in vitro.EBV-associated lymphomas most commonly occur in patients who areseverely immunosuppressed and hence do not use immune evasionstrategies. We have shown that these tumors can be treated effectivelywith infusions of virus-specific CTLs. The tumors occurring in patientswho are immunocompetent or only mildly immunosuppressed do employ immuneevasion strategies and these provide a model for the use of CTLs thathave been genetically modified to persist and function under adverseconditions.