Cargando…

Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant

OBJECTIVES: Adoptive immunotherapy using donor‐derived antigen‐specific T‐cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT). METHODS: We treated 11 patients with a prophylactic infusion of 2 × 10(7) cells per square metre donor‐derived T‐cells targeting...

Descripción completa

Detalles Bibliográficos
Autores principales: Gottlieb, David Jonathan, Clancy, Leighton Edward, Withers, Barbara, McGuire, Helen Marie, Luciani, Fabio, Singh, Mandeep, Hughes, Brendan, Gloss, Brian, Kliman, David, Ma, Chun Kei Kris, Panicker, Shyam, Bishop, David, Dubosq, Ming‐Celine, Li, Ziduo, Avdic, Selmir, Micklethwaite, Kenneth, Blyth, Emily
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960021/
https://www.ncbi.nlm.nih.gov/pubmed/33747509
http://dx.doi.org/10.1002/cti2.1249
_version_ 1783665050334003200
author Gottlieb, David Jonathan
Clancy, Leighton Edward
Withers, Barbara
McGuire, Helen Marie
Luciani, Fabio
Singh, Mandeep
Hughes, Brendan
Gloss, Brian
Kliman, David
Ma, Chun Kei Kris
Panicker, Shyam
Bishop, David
Dubosq, Ming‐Celine
Li, Ziduo
Avdic, Selmir
Micklethwaite, Kenneth
Blyth, Emily
author_facet Gottlieb, David Jonathan
Clancy, Leighton Edward
Withers, Barbara
McGuire, Helen Marie
Luciani, Fabio
Singh, Mandeep
Hughes, Brendan
Gloss, Brian
Kliman, David
Ma, Chun Kei Kris
Panicker, Shyam
Bishop, David
Dubosq, Ming‐Celine
Li, Ziduo
Avdic, Selmir
Micklethwaite, Kenneth
Blyth, Emily
author_sort Gottlieb, David Jonathan
collection PubMed
description OBJECTIVES: Adoptive immunotherapy using donor‐derived antigen‐specific T‐cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT). METHODS: We treated 11 patients with a prophylactic infusion of 2 × 10(7) cells per square metre donor‐derived T‐cells targeting seven infections (six viral and one fungal) following HSCT. Targeted pathogens were cytomegalovirus (CMV), Epstein–Barr virus (EBV), adenovirus, varicella zoster virus, influenza, BK virus (BKV) and Aspergillus fumigatus. RESULTS: T‐cell products were successfully generated in all patients with 10 products responsive to 6 or 7 infections. T‐cell infusions were associated with increases in antigen‐experienced activated CD8(+) T‐cells by day 30. CMV, EBV and BKV reactivation occurred in the majority of patients and was well controlled except where glucocorticoids were administered soon after T‐cell infusion. Three patients in that circumstance developed CMV tissue infection. No patient required treatment for invasive fungal infection. The most common CMV and EBV TCR clonotypes in the infusion product became the most common clonotypes seen at day 30 post‐T‐cell infusion. Donors and their recipients were recruited to the study prior to transplant. Grade III/IV graft‐versus‐host disease developed in four patients. At a median follow‐up of 390 days post‐transplant, six patients had died, 5 of relapse, and 1 of multi‐organ failure. Infection did not contribute to death in any patient. CONCLUSION: Rapid reconstitution of immunity to a broad range of viral and fungal infections can be achieved using a multi‐pathogen‐specific T‐cell product. The development of GVHD after T‐cell infusion suggests that infection‐specific T‐cell therapy after allogeneic stem cell transplant should be combined with other strategies to reduce graft‐versus‐host disease.
format Online
Article
Text
id pubmed-7960021
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-79600212021-03-19 Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant Gottlieb, David Jonathan Clancy, Leighton Edward Withers, Barbara McGuire, Helen Marie Luciani, Fabio Singh, Mandeep Hughes, Brendan Gloss, Brian Kliman, David Ma, Chun Kei Kris Panicker, Shyam Bishop, David Dubosq, Ming‐Celine Li, Ziduo Avdic, Selmir Micklethwaite, Kenneth Blyth, Emily Clin Transl Immunology Original Article OBJECTIVES: Adoptive immunotherapy using donor‐derived antigen‐specific T‐cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT). METHODS: We treated 11 patients with a prophylactic infusion of 2 × 10(7) cells per square metre donor‐derived T‐cells targeting seven infections (six viral and one fungal) following HSCT. Targeted pathogens were cytomegalovirus (CMV), Epstein–Barr virus (EBV), adenovirus, varicella zoster virus, influenza, BK virus (BKV) and Aspergillus fumigatus. RESULTS: T‐cell products were successfully generated in all patients with 10 products responsive to 6 or 7 infections. T‐cell infusions were associated with increases in antigen‐experienced activated CD8(+) T‐cells by day 30. CMV, EBV and BKV reactivation occurred in the majority of patients and was well controlled except where glucocorticoids were administered soon after T‐cell infusion. Three patients in that circumstance developed CMV tissue infection. No patient required treatment for invasive fungal infection. The most common CMV and EBV TCR clonotypes in the infusion product became the most common clonotypes seen at day 30 post‐T‐cell infusion. Donors and their recipients were recruited to the study prior to transplant. Grade III/IV graft‐versus‐host disease developed in four patients. At a median follow‐up of 390 days post‐transplant, six patients had died, 5 of relapse, and 1 of multi‐organ failure. Infection did not contribute to death in any patient. CONCLUSION: Rapid reconstitution of immunity to a broad range of viral and fungal infections can be achieved using a multi‐pathogen‐specific T‐cell product. The development of GVHD after T‐cell infusion suggests that infection‐specific T‐cell therapy after allogeneic stem cell transplant should be combined with other strategies to reduce graft‐versus‐host disease. John Wiley and Sons Inc. 2021-03-15 /pmc/articles/PMC7960021/ /pubmed/33747509 http://dx.doi.org/10.1002/cti2.1249 Text en © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Article
Gottlieb, David Jonathan
Clancy, Leighton Edward
Withers, Barbara
McGuire, Helen Marie
Luciani, Fabio
Singh, Mandeep
Hughes, Brendan
Gloss, Brian
Kliman, David
Ma, Chun Kei Kris
Panicker, Shyam
Bishop, David
Dubosq, Ming‐Celine
Li, Ziduo
Avdic, Selmir
Micklethwaite, Kenneth
Blyth, Emily
Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant
title Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant
title_full Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant
title_fullStr Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant
title_full_unstemmed Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant
title_short Prophylactic antigen‐specific T‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant
title_sort prophylactic antigen‐specific t‐cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960021/
https://www.ncbi.nlm.nih.gov/pubmed/33747509
http://dx.doi.org/10.1002/cti2.1249
work_keys_str_mv AT gottliebdavidjonathan prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT clancyleightonedward prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT withersbarbara prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT mcguirehelenmarie prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT lucianifabio prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT singhmandeep prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT hughesbrendan prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT glossbrian prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT klimandavid prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT machunkeikris prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT panickershyam prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT bishopdavid prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT dubosqmingceline prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT liziduo prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT avdicselmir prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT micklethwaitekenneth prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant
AT blythemily prophylacticantigenspecifictcellstargetingsevenviralandfungalpathogensafterallogeneichaemopoieticstemcelltransplant