Principles for Adoptive T Cell Therapy of Human Viral Diseases

Abstract

The development of successful adoptive immunotherapy for human virus infections is predicated on an understanding of the effector cells and mechanisms essential for providing the host with a protective response to acute infection and the requirements for long-term in vivo survival of transferred cells that will be necessary to provide memory responses to persistent and latent viral infections. In this review, we discuss the results of recent studies examining the effector mechanisms mediated by virus-specific αβ+ T cells and the strategies viruses have evolved to evade recognition by such T cells and/or to interfere with the expression of T cell effector functions. The evasion strategies employed by individual viruses can render T cell subsets or T cells of particular specificities less effective in eliminating virally infected cells, and consequently they are less desirable choices for use in adoptive therapy. Insights derived from described studies of the pathogenesis and immunobiology of virus infections have resulted in the development of clinical adoptive immunotherapy studies for infections with CMV, EBV, and HIV. Although the results from such studies are preliminary, the principle that virus-specific T cells can be successfully transferred and can mediate therapeutic efficacy in humans has already been affirmed. The use of recently developed methods, such as retroviral-mediated gene transfer, to genetically modify antigen-specific T cell clones provides a novel approach to overcome limitations and improve on the safety and efficacy observed in these initial studies, suggesting that more widespread use of adoptive transfer of specific T cells as a therapeutic regimen should be feasible in the near future.