T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy

A range of emerging therapeutic approaches for the treatment of cancer aim to induce or augment endogenous T cell responses. Chimeric antigen receptor (CAR) T cell therapy (CTT) is one such approach that utilises the patient’s own T cells, engineered ex vivo to target cell surface antigens, to elimi...

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Autores principales:	Palak H. Mehta, Salvatore Fiorenza, Rachel M. Koldej, Anthony Jaworowski, David S. Ritchie, Kylie M. Quinn
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	T cell fitness CAR T cell haematological cancer ageing inflammation kinase inhibitor Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/aadff898576844feb5cfd0a605822392
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spelling	oai:doaj.org-article:aadff898576844feb5cfd0a6058223922021-12-01T03:37:04ZT Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy1664-322410.3389/fimmu.2021.780442https://doaj.org/article/aadff898576844feb5cfd0a6058223922021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.780442/fullhttps://doaj.org/toc/1664-3224A range of emerging therapeutic approaches for the treatment of cancer aim to induce or augment endogenous T cell responses. Chimeric antigen receptor (CAR) T cell therapy (CTT) is one such approach that utilises the patient’s own T cells, engineered ex vivo to target cell surface antigens, to eliminate haematological malignancies. Despite mediating high rates of responses in some clinical trials, this approach can be limited by dysfunctional T cells if they are present at high frequencies either in the starting material from the patient or the CAR T cell product. The fitness of an individual’s T cells, driven by age, chronic infection, disease burden and cancer treatment, is therefore likely to be a crucial limiting factor of CTT. Currently, T cell dysfunction and its impact on CTT is not specifically quantified when patients are considering the therapy. Here, we review our current understanding of T cell fitness for CTT, how fitness may be impacted by age, chronic infection, malignancy, and treatment. Finally, we explore options to specifically tailor clinical decision-making and the CTT protocol for patients with more extensive dysfunction to improve treatment efficacy. A greater understanding of T cell fitness throughout a patient’s treatment course could ultimately be used to identify patients likely to achieve favourable CTT outcomes and improve methods for T cell collection and CTT delivery.Palak H. MehtaSalvatore FiorenzaRachel M. KoldejRachel M. KoldejAnthony JaworowskiDavid S. RitchieDavid S. RitchieKylie M. QuinnKylie M. QuinnFrontiers Media S.A.articleT cell fitnessCAR T cellhaematological cancerageinginflammationkinase inhibitorImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	T cell fitness CAR T cell haematological cancer ageing inflammation kinase inhibitor Immunologic diseases. Allergy RC581-607
spellingShingle	T cell fitness CAR T cell haematological cancer ageing inflammation kinase inhibitor Immunologic diseases. Allergy RC581-607 Palak H. Mehta Salvatore Fiorenza Rachel M. Koldej Rachel M. Koldej Anthony Jaworowski David S. Ritchie David S. Ritchie Kylie M. Quinn Kylie M. Quinn T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy
description	A range of emerging therapeutic approaches for the treatment of cancer aim to induce or augment endogenous T cell responses. Chimeric antigen receptor (CAR) T cell therapy (CTT) is one such approach that utilises the patient’s own T cells, engineered ex vivo to target cell surface antigens, to eliminate haematological malignancies. Despite mediating high rates of responses in some clinical trials, this approach can be limited by dysfunctional T cells if they are present at high frequencies either in the starting material from the patient or the CAR T cell product. The fitness of an individual’s T cells, driven by age, chronic infection, disease burden and cancer treatment, is therefore likely to be a crucial limiting factor of CTT. Currently, T cell dysfunction and its impact on CTT is not specifically quantified when patients are considering the therapy. Here, we review our current understanding of T cell fitness for CTT, how fitness may be impacted by age, chronic infection, malignancy, and treatment. Finally, we explore options to specifically tailor clinical decision-making and the CTT protocol for patients with more extensive dysfunction to improve treatment efficacy. A greater understanding of T cell fitness throughout a patient’s treatment course could ultimately be used to identify patients likely to achieve favourable CTT outcomes and improve methods for T cell collection and CTT delivery.
format	article
author	Palak H. Mehta Salvatore Fiorenza Rachel M. Koldej Rachel M. Koldej Anthony Jaworowski David S. Ritchie David S. Ritchie Kylie M. Quinn Kylie M. Quinn
author_facet	Palak H. Mehta Salvatore Fiorenza Rachel M. Koldej Rachel M. Koldej Anthony Jaworowski David S. Ritchie David S. Ritchie Kylie M. Quinn Kylie M. Quinn
author_sort	Palak H. Mehta
title	T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy
title_short	T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy
title_full	T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy
title_fullStr	T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy
title_full_unstemmed	T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy
title_sort	t cell fitness and autologous car t cell therapy in haematologic malignancy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/aadff898576844feb5cfd0a605822392
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T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy

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