Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review

Abstract

Opportunistic viral infections of the central nervous system represent a significant cause of morbidity and mortality among an increasing number of immunocompromised patients. Since antiviral treatments are usually poorly effective, the prognosis generally relies on the ability to achieve timely immune reconstitution. Hence, strategies aimed at reinvigorating antiviral immune activity have recently emerged. Among these, virus-specific T-cells are increasingly perceived as a principled and valuable tool to treat opportunistic viral infections. Here we briefly discuss how to develop and select virus-specific T-cells, then review their main indications in central nervous system infections, including progressive multifocal leukoencephalopathy, CMV infection, and adenovirus infection. We also discuss their potential interest in the treatment of progressive multiple sclerosis, or EBV-associated central nervous system inflammatory disease. We finish with the key future milestones of this promising treatment strategy.

Keywords: T-cell transfer; adenovirus; cellular therapy; central nervous system; cytomegalovirus; encephalitis; immune therapy; multiple sclerosis; progressive multifocal leukoencephalopathy; viral infections; virus-specific T-cells.

Figure 1

Methods used to produce virus-specific T-cells. First, blood is collected from the T-cell donor, which can be either the patient themself, the transplant donor in the case of hematopoietic stem cell donor, or a third party. Peripheral blood mononuclear cells (PBMCs) are isolated. These can be cultured in vitro for several days to weeks in the presence of virus antigens to produce large amounts of cells that will be infused to the patient but will usually expand only moderately in vivo. Another approach is the direct selection of virus-specific T-cells from the collected PBMCs. Several methods exist for this process, the most widely used being the cytokine-capture method, described in the text. After selection of a limited number of specific T-cells, these are infused to the patient where they can expand extensively.

Figure 2

Use of adoptive virus-specific T-cell therapy in affections of the central nervous system. Central nervous system affections for which the use of virus-specific T-cell therapy has been reported are represented in this figure. The graph on the right shows the number of cases reported per virus. HAdV = adenovirus; CMV = cytomegalovirus; EBV = Epstein–Barr virus; HPyV2 = Human polyomavirus 2; PML = progressive multifocal leukoencephalopathy; VSTs = virus-specific T-cells.