Adoptive transfer of polyclonal, EBV-specific cytotoxic T-cell lines for the prevention and treatment of EBV-associated malignancies

There is increasing: interest in using adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTL) for the treatment of cancer. The challenges facing this strategy include identification of tumor antigens against which to target CTLs, the development of methods to activate and expand tumor-specific CTLs in vitro, and ensuring the in vivo survival and function of the CTLs in the face of multiple antiimmune response strategies employed by viruses and tumors. Epstein-Barr virus (EBV) provides ideal model systems in which to test the safety and efficacy of infusions of virus-specific CTLs for the treatment of tumors with and without immune evasion strategies. EBV-transformed B-cell lines (LCLs) are excellent antigen-presenting cells (APCs) that express nine virus-encoded proteins and can be used to stimulate and expand EBV-specific CTL lines from most donors in vitro. EBV-associated lymphomas most commonly occur in patients who are severely immunosuppressed and hence do not use immune evasion strategies. We have shown that these tumors can be treated effectively with infusions of virus-specific CTLs. The tumors occurring in patients who are immunocompetent or only mildly immunosuppressed do employ immune evasion strategies and these provide a model for the use of CTLs that have been genetically modified to persist and function under adverse conditions.