Strategies to harness immunity against infectious pathogens after haploidentical stem cell transplantation

Viral and fungal infections account for significant morbidity and mortality, particularly in pediatric patients with profound immune suppression resulting from allogeneic hematopoietic stem cell transplantation (HSCT). Therapies with anti-viral and anti-fungal drugs are often associated with significant toxicity, are of limited efficacy and can induce drug resistance. One innovative approach to prevent and/or treat viral and fungal infections involves the adoptive transfer of in vitro-expanded or in vitro-generated pathogen-specific T cells. This review summarizes the clinical trials that have been run to date with virus- and fungus-specific T cells, with special emphasis on the clinical context of haploidentical HSCT for pediatric malignancies. It will also discuss initiatives and strategies to overcome the hurdles associated with time-consuming and complex GMP-grade laboratory procedures required to generate pathogen-specific T cells.