Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow

T cell based immunotherapies can be applicable to acute myeloid leukemia (AML). Therefore, the selection of optimal T cells, cell manufacturing, and therapeutic T cell engineering are essential for the development of effective adoptive T cell therapies for AML. Autologous tumor-infiltrating lymphocy...

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Autores principales:	Huynh Cao, Do Hyun Kim, Ashley Howard, Hector Moz, Samiksha Wasnik, David J. Baylink, Chien-Shing Chen, Mark E Reeves, Saied Mirshahidi, Jeffrey Xiao, Olivia Francis, Guido Marcucci, Yi Xu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Acute myeloid leukemia Tumor-Infiltrating Lymphocytes Immunotherapy Naïve T CCR7 CD95 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/207d9563c96c4f869249a88fd26308d6
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spelling	oai:doaj.org-article:207d9563c96c4f869249a88fd26308d62021-11-30T04:14:39ZEx vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow1476-558610.1016/j.neo.2021.11.003https://doaj.org/article/207d9563c96c4f869249a88fd26308d62021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1476558621000932https://doaj.org/toc/1476-5586T cell based immunotherapies can be applicable to acute myeloid leukemia (AML). Therefore, the selection of optimal T cells, cell manufacturing, and therapeutic T cell engineering are essential for the development of effective adoptive T cell therapies for AML. Autologous tumor-infiltrating lymphocytes (TILs) have been in clinical trials to treat solid malignancies. Herein, we assessed whether TILs can be isolated from the bone marrow (BM) of AML patients, expanded ex vivo and utilized as a novel therapeutic strategy for AML. To this end, firstly we analyzed the immunophenotypes of a series of primary BM samples from AML patients (N = 10) by flow cytometry. We observed a variable amount of CD3+ TILs (range ∼2.3–∼32.6% of mononuclear cells) among BM samples. We then developed a novel protocol that produced a three-log ex vivo expansion of TILs isolated from AML patient BM (N = 10) and peripheral blood (PB) (N = 10), including from patients with a low number of CD3+ T cells, within 3, 4 weeks. Further, we identified previously described naïve T cells (CCR7+CD95-/or CD62L+CD45RA+) in AML BM and PB samples, which seemed to be required for a successful TILs ex vivo expansion. Finally, we showed that the expanded TILs could: (1) cause cytotoxicity to autologous AML blasts ex vivo (90.6% in control without T cell treatment vs. 1.89% in experimental groups with PB derived T cells and 1.77% in experimental groups with BM derived TILs, p < 0.01), (2) be genetically engineered to express CYP27B1 gene, and (3) infiltrate the BM and reside in close proximity to pre-injected autologous AML blasts of engrafted immunodeficiency mice. Altogether, these results provide a rationale for further studies of the therapeutic use of TILs in AML.Huynh CaoDo Hyun KimAshley HowardHector MozSamiksha WasnikDavid J. BaylinkChien-Shing ChenMark E ReevesSaied MirshahidiJeffrey XiaoOlivia FrancisGuido MarcucciYi XuElsevierarticleAcute myeloid leukemiaTumor-Infiltrating LymphocytesImmunotherapyNaïve TCCR7CD95Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENNeoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1252-1260 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acute myeloid leukemia Tumor-Infiltrating Lymphocytes Immunotherapy Naïve T CCR7 CD95 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Acute myeloid leukemia Tumor-Infiltrating Lymphocytes Immunotherapy Naïve T CCR7 CD95 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Huynh Cao Do Hyun Kim Ashley Howard Hector Moz Samiksha Wasnik David J. Baylink Chien-Shing Chen Mark E Reeves Saied Mirshahidi Jeffrey Xiao Olivia Francis Guido Marcucci Yi Xu Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
description	T cell based immunotherapies can be applicable to acute myeloid leukemia (AML). Therefore, the selection of optimal T cells, cell manufacturing, and therapeutic T cell engineering are essential for the development of effective adoptive T cell therapies for AML. Autologous tumor-infiltrating lymphocytes (TILs) have been in clinical trials to treat solid malignancies. Herein, we assessed whether TILs can be isolated from the bone marrow (BM) of AML patients, expanded ex vivo and utilized as a novel therapeutic strategy for AML. To this end, firstly we analyzed the immunophenotypes of a series of primary BM samples from AML patients (N = 10) by flow cytometry. We observed a variable amount of CD3+ TILs (range ∼2.3–∼32.6% of mononuclear cells) among BM samples. We then developed a novel protocol that produced a three-log ex vivo expansion of TILs isolated from AML patient BM (N = 10) and peripheral blood (PB) (N = 10), including from patients with a low number of CD3+ T cells, within 3, 4 weeks. Further, we identified previously described naïve T cells (CCR7+CD95-/or CD62L+CD45RA+) in AML BM and PB samples, which seemed to be required for a successful TILs ex vivo expansion. Finally, we showed that the expanded TILs could: (1) cause cytotoxicity to autologous AML blasts ex vivo (90.6% in control without T cell treatment vs. 1.89% in experimental groups with PB derived T cells and 1.77% in experimental groups with BM derived TILs, p < 0.01), (2) be genetically engineered to express CYP27B1 gene, and (3) infiltrate the BM and reside in close proximity to pre-injected autologous AML blasts of engrafted immunodeficiency mice. Altogether, these results provide a rationale for further studies of the therapeutic use of TILs in AML.
format	article
author	Huynh Cao Do Hyun Kim Ashley Howard Hector Moz Samiksha Wasnik David J. Baylink Chien-Shing Chen Mark E Reeves Saied Mirshahidi Jeffrey Xiao Olivia Francis Guido Marcucci Yi Xu
author_facet	Huynh Cao Do Hyun Kim Ashley Howard Hector Moz Samiksha Wasnik David J. Baylink Chien-Shing Chen Mark E Reeves Saied Mirshahidi Jeffrey Xiao Olivia Francis Guido Marcucci Yi Xu
author_sort	Huynh Cao
title	Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
title_short	Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
title_full	Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
title_fullStr	Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
title_full_unstemmed	Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
title_sort	ex vivo isolation, expansion and bioengineering of ccr7+cd95-/or cd62l+cd45ra+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/207d9563c96c4f869249a88fd26308d6
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Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow

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