Gaurav Sutrave1,2, David J Gottlieb1,2,3. 1. Department of Haematology, Westmead Hospital. 2. Westmead Institute for Medical Research, The University of Sydney. 3. Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Sydney, Australia.
Abstract
PURPOSE OF REVIEW: Viral and fungal infections cause significant morbidity and mortality following hematopoietic stem-cell transplantation (HSCT), primarily due to the prolonged and complex immunodeficient state that results from conditioning chemo-radiotherapy and subsequent prophylaxis of graft vs. host disease. Although currently available antimicrobial pharmacotherapies have demonstrated short-term efficacy, their toxicities often preclude long-term use, and cessation if frequently associated with recurrent infection. Adoptive cell therapy (ACT) offers the potential to more rapidly reconstitute antimicrobial immune responses in the posttransplant setting. RECENT FINDINGS: Traditional approaches to manufacture of adoptive T-cell therapies are time consuming and limited to single pathogen specificity. Recent advances in the understanding of immunogenic epitopes, improved methods for pathogen-specific T-cell isolation and cultureware technologies is allowing for rapid generation of ACTs for clinical use. SUMMARY: The current review summarizes the potential infectious targets and manufacturing methodologies for ACTs and contrasts their clinical efficacy and safety to currently available pharmacotherapies for patients recovering after HSCT.
PURPOSE OF REVIEW: Viral and fungal infections cause significant morbidity and mortality following hematopoietic stem-cell transplantation (HSCT), primarily due to the prolonged and complex immunodeficient state that results from conditioning chemo-radiotherapy and subsequent prophylaxis of graft vs. host disease. Although currently available antimicrobial pharmacotherapies have demonstrated short-term efficacy, their toxicities often preclude long-term use, and cessation if frequently associated with recurrent infection. Adoptive cell therapy (ACT) offers the potential to more rapidly reconstitute antimicrobial immune responses in the posttransplant setting. RECENT FINDINGS: Traditional approaches to manufacture of adoptive T-cell therapies are time consuming and limited to single pathogen specificity. Recent advances in the understanding of immunogenic epitopes, improved methods for pathogen-specific T-cell isolation and cultureware technologies is allowing for rapid generation of ACTs for clinical use. SUMMARY: The current review summarizes the potential infectious targets and manufacturing methodologies for ACTs and contrasts their clinical efficacy and safety to currently available pharmacotherapies for patients recovering after HSCT.
Authors: Derek J Hanson; Hu Xie; Danielle M Zerr; Wendy M Leisenring; Keith R Jerome; Meei-Li Huang; Terry Stevens-Ayers; Michael Boeckh; David M Koelle; Joshua A Hill Journal: J Infect Dis Date: 2021-02-24 Impact factor: 5.226