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T-Cell Immune Therapies
Cellular therapies designed to modulate or enhance immune responses are gaining acceptance as viable treatments for a variety of diseases, most notably in the oncology field. Some therapies such as granulocyte infusion have been a tool in transfusion medicine for more than 40 years, while novel therapies such as chimeric antigen receptor (CAR) T cells have only very recently been licensed for clinical use. This chapter will focus on T cell–based immunotherapy. Mechanistically, T-cell immune therapies range in function from replacing missing immune cells after chemotherapy (antiviral T-cell therapy), to augmenting or redirecting T-cell responses against tumors (tumor-infiltrating lymphocytes, or TILS, and CAR T cells), to modulating the systemic immune response in the case of regulatory T cells (Tregs). While the promise of T cell–based immune therapies is clear, the final determination of their benefit and the role transfusion medicine will play in providing these novel therapies is not defined and will depend on institutional resources and expertise.
T Cells as Immune Therapeutics
T cells are key members of the adaptive immune response, with effector functions that include cytokine secretion, promotion of antibody responses, and killing virus-infected or tumor cells. In addition, some T cells play a role in damping down immune responses, such as Tregs that can inhibit both T-cell and B-cell function. As adoptive immune therapy, T cells have been used to treat a variety of cancers, as well as to treat or prevent viral infections ( Table 87.1 ). As opposed to transfer of effector/killer T cells, Treg cells can counteract a variety of inflammatory conditions. The best studied of these is as prevention or treatment of graft-versus-host disease (GVHD), and trials have been performed for the treatment of autoimmune disease or to build tolerance in organ transplantation.
Table 87.1
T-Cell Immunotherapies
| Disease | Therapy | Progress |
|---|---|---|
| Tumor eradication | CAR T cells | FDA approved |
| Tumor eradication | Tumor-infiltrating lymphocytes | Phase 1 through 3 trials |
| Tumor eradication | Enhanced affinity T-cell receptor | Phase 1 and 2 trials |
| Viral infections posthematopoietic stem cell transplantation | Effector T-cell transfer | Phase 1 through 3 trials |
| Graft-versus-host disease | Treg transfer | Phase 1 and 2 trials |
| Autoimmunity | Treg transfer | Phase 1 and 2 trials |
| Organ transplantation | Treg transfer | Phase 1 and 2 trials |
Antiviral Cellular Therapy and Prophylaxis
Viral infections normally controlled by the immune system are frequently lethal in settings of profound T-cell depletion, such as after allogeneic hematopoietic stem cell transplantation (HSCT). Examples of problematic viruses include infection with the chronic viruses, cytomegalovirus and Epstein–Barr virus and the acute virus adenovirus. One solution to preventing or treating viral infection after HSCT is to infuse donor lymphocytes. Efficacy of infusion of unselected donor lymphocytes is limited by the typical low frequency of virus-specific T cells in the population and the side effect of increased alloreactive T cells and frequency of GVHD. The therapeutic index of donor lymphocytes can be improved through depletion of alloreactive T cells and enrichment for virus-specific T cells. Techniques used to enrich for these cells include selecting for cells of known specificity using multimers of peptide-MHC, stimulating cells with viral peptide and capturing those that secrete interferon-γ, or expanding virus-specific cells in vitro.
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