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Antigen-specific T cells, which recognize processed fragments of proteins presented in association with major histocompatibility complex molecules, represent an important component of the host response to pathogens and tumors. Adoptive T-cell therapy, in which T cells are administered to augment or establish an immune response, shows efficacy for the treatment of infectious and malignant diseases. The clinical application of T-cell transfer has been facilitated by identification of target antigens expressed by viruses and tumors, improved strategies for the isolation and genetic engineering of antigen-specific T cells with intrinsic qualities that enable their persistence in vivo, and the recognition that transferring T cells into a lymphopenic environment improves the efficiency of cell transfer and treatment efficacy. The development of cell based vaccines that can elicit a tumor-reactive T-cell response in vivo to treat cancer remains an area of investigation. Dendritic cells (DCs) are specialized antigen-presenting cells that elicit and regulate specific T-cell responses. Strategies that employ DCs that have taken up tumor antigens in vitro as vaccines or that target antigen to DCs in vivo to elicit a response are being investigated. Insight into the obstacles to routinely achieving an effective antitumor response either by T-cell therapy or vaccination have been derived from careful analysis of clinical trials, and it is likely that further development of immune cell therapy will be combined with interventions that target specific regulatory or inhibitory pathways.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: APC, antigen-presenting cell; cDNA, complementary DNA; CML, chronic myelogenous leukemia; CMV, cytomegalovirus; CTL, cytotoxic T lymphocyte; DC, dendritic cell; EBV, Epstein-Barr virus; GVHD, graft-versus-host disease; GVL, graft-versus-leukemia; HSCT, hematopoietic stem cell transplantation; LPD, lymphoproliferative disease; mAbs, monoclonal antibodies; mHAgs, minor histocompatibility antigens; MHC, major histocompatability complex; PBMC, peripheral blood mononuclear cells; SNP, single nucleotide polymorphism; TCR, T-cell receptor; Th, T helper; TIL, tumor-infiltrating lymphocyte.

Two broad subsets of antigen-specific T cells cooperate to terminate acute viral infections and control reactivation of latent viruses. CD8+ cytotoxic T lymphocytes (CTLs) recognize viral peptides presented by major histocompatibility complex (MHC) class I molecules and lyse infected cells, and produce inflammatory cytokines. CD4+ T-helper (Th) cells recognize viral peptides presented by class II MHC molecules and produce cytokines that amplify T-cell responses or promote B-cell proliferation and antibody production. A deficiency of CD8+ and CD4+ T cells occurs after allogeneic hematopoietic stem cell transplantation (HSCT) as a consequence of the administration of intensive chemoradiotherapy, anti–T-cell monoclonal antibodies (mAbs), and/or immunosuppressive drugs, and these patients are at risk for life-threatening viral infection.1 T-cell therapy for human viruses requires knowledge of the antigens presented by infected cells, strategies for isolating and propagating T cells of the appropriate phenotype and specificity, and methods for monitoring the in vivo activity of transferred cells (Fig. 24–1). Clinical trials have now established that adoptive T-cell therapy has antiviral activity against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus infection in immunocompromised allogeneic ...

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