TY - JOUR
T1 - Harnessing T Cells to Control Infections After Allogeneic Hematopoietic Stem Cell Transplantation
AU - Basso, Sabrina
AU - Compagno, Francesca
AU - Zelini, Paola
AU - Giorgiani, Giovanna
AU - Boghen, Stella
AU - Bergami, Elena
AU - Bagnarino, Jessica
AU - Siciliano, Mariangela
AU - Del Fante, Claudia
AU - Luppi, Mario
AU - Zecca, Marco
AU - Comoli, Patrizia
N1 - Funding Information:
This work was supported by grants from the Fondazione Regionale per la Ricerca Biomedica (PC), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo [Ricerca Corrente 08069113 and 08069119 (PC); Ricerca Corrente 08045818 (MZ); Ricerca Corrente 08071519 (SBa)], Fondazione Just Italia (PC), Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy (IG 20624-2018) (ML), and the “Charity Dinner Initiative” in memory of Dr. A. Fontana for Associazione Italiana Lotta alle Leucemie, Linfoma e Mieloma (AIL) – Sezione ‘Luciano Pavarotti’– Modena-ONLUS (ML).
Publisher Copyright:
© Copyright © 2020 Basso, Compagno, Zelini, Giorgiani, Boghen, Bergami, Bagnarino, Siciliano, Del Fante, Luppi, Zecca and Comoli.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/15
Y1 - 2020/10/15
N2 - Dramatic progress in the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from alternative sources in pediatric patients has been registered over the past decade, providing a chance to cure children and adolescents in need of a transplant. Despite these advances, transplant-related mortality due to infectious complications remains a major problem, principally reflecting the inability of the depressed host immune system to limit infection replication and dissemination. In addition, development of multiple infections, a common occurrence after high-risk allo-HSCT, has important implications for overall survival. Prophylactic and preemptive pharmacotherapy is limited by toxicity and, to some extent, by lack of efficacy in breakthrough infections. T-cell reconstitution is a key requirement for effective infection control after HSCT. Consequently, T-cell immunotherapeutic strategies to boost pathogen-specific immunity may complement or represent an alternative to drug treatments. Pioneering proof of principle studies demonstrated that the administration of donor-derived T cells directed to human herpesviruses, on the basis of viral DNA monitoring, could effectively restore specific immunity and confer protection against viral infections. Since then, the field has evolved with implementation of techniques able to hasten production, allow for selection of specific cell subsets, and target multiple pathogens. This review provides a brief overview of current cellular therapeutic strategies to prevent or treat pathogen-related complications after HSCT, research carried out to increase efficacy and safety, including T-cell production for treatment of infections in patients with virus-naïve donors, results from clinical trials, and future developments to widen adoptive T-cell therapy access in the HSCT setting.
AB - Dramatic progress in the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from alternative sources in pediatric patients has been registered over the past decade, providing a chance to cure children and adolescents in need of a transplant. Despite these advances, transplant-related mortality due to infectious complications remains a major problem, principally reflecting the inability of the depressed host immune system to limit infection replication and dissemination. In addition, development of multiple infections, a common occurrence after high-risk allo-HSCT, has important implications for overall survival. Prophylactic and preemptive pharmacotherapy is limited by toxicity and, to some extent, by lack of efficacy in breakthrough infections. T-cell reconstitution is a key requirement for effective infection control after HSCT. Consequently, T-cell immunotherapeutic strategies to boost pathogen-specific immunity may complement or represent an alternative to drug treatments. Pioneering proof of principle studies demonstrated that the administration of donor-derived T cells directed to human herpesviruses, on the basis of viral DNA monitoring, could effectively restore specific immunity and confer protection against viral infections. Since then, the field has evolved with implementation of techniques able to hasten production, allow for selection of specific cell subsets, and target multiple pathogens. This review provides a brief overview of current cellular therapeutic strategies to prevent or treat pathogen-related complications after HSCT, research carried out to increase efficacy and safety, including T-cell production for treatment of infections in patients with virus-naïve donors, results from clinical trials, and future developments to widen adoptive T-cell therapy access in the HSCT setting.
KW - Allo-HSCT
KW - multipathogen infection
KW - pathogen specific T cells
KW - T cell immunity
KW - T-cell therapy
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U2 - 10.3389/fimmu.2020.567531
DO - 10.3389/fimmu.2020.567531
M3 - Review article
C2 - 33178192
AN - SCOPUS:85094820917
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 567531
ER -