Administration of CD4+CD25highCD127−FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study
Background Multiple sclerosis (MS) is an immune-mediated disease in which autoimmune T conventional (T conv ) cells break the blood–brain barrier and destroy neurons of the central nervous system. It is hypothesized that CD4 + CD25 high CD127 − FoxP3 + T regulatory (T reg ) cells may inhibit this de...
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| Veröffentlicht in: | BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy biopharmaceuticals, and gene therapy, 2021, Vol.35 (1), p.47-60 |
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| creator | Chwojnicki, Kamil Iwaszkiewicz-Grześ, Dorota Jankowska, Anna Zieliński, Maciej Łowiec, Paweł Gliwiński, Mateusz Grzywińska, Małgorzata Kowalczyk, Kamil Konarzewska, Aleksandra Glasner, Paulina Sakowska, Justyna Kulczycka, Julia Jaźwińska-Curyłło, Anna Kubach, Marlena Karaszewski, Bartosz Nyka, Walenty Szurowska, Edyta Trzonkowski, Piotr |
| description | Background
Multiple sclerosis (MS) is an immune-mediated disease in which autoimmune T conventional (T
conv
) cells break the blood–brain barrier and destroy neurons of the central nervous system. It is hypothesized that CD4
+
CD25
high
CD127
−
FoxP3
+
T regulatory (T
reg
) cells may inhibit this destruction through suppressive activity exerted on T
conv
cells.
Methods
We present the results of a phase 1b/2a, open-label, two-arm clinical trial in 14 patients treated with autologous T
reg
cells for relapsing-remitting MS. The patients received either expanded ex vivo T
reg
cells intravenously (intravenous [IV] group,
n
= 11; dose 40 × 10
6
T
reg
cells/kg of body weight) or freshly isolated T
reg
cells intrathecally (intrathecal [IT] group,
n
= 3; dose 1.0 × 10
6
T
reg
cells). Importantly, patients were not treated with any other disease-modifying drugs for at least 6 months before the recruitment and during the follow-up.
Results
No severe adverse events were observed. Self-assessed quality of life (EuroQol–5 Dimensions [EQ-5D] form) did not change and did not differ significantly between the groups. A total of 12 relapses were noted in five intravenously treated patients, who had from one to three attacks per year. Three out of ten participants who completed the trial in the IV group deteriorated more than 1 point on the Expanded Disability Status Scale (EDSS) during the follow-up. At the same time, no patients in the IT group experienced a relapse or such a deterioration in the EDSS. No significant differences were found in the Multiple Sclerosis Functional Composite (MSFC) scale in both the IV and IT groups. Magnetic resonance imaging (MRI) scans revealed a significantly lower change in the T2 lesion volume in the IT group compared to the IV group. The increase in the number of new T2 lesions during the follow-up was significant for the IV group only. There were no significant changes in the level of T
reg
cells or T
conv
cells in the peripheral blood throughout the follow-up or between the groups. Interestingly, T
reg
cells in all patients consisted of two different phenotypes: peripheral T
reg
cells Helios(−) (≈ 20%) and thymic T
reg
cells Helios(+) (≈ 80%). The analysis of the cytokine pattern revealed higher levels of transforming growth factor-α and proinflammatory factors MCP3, CXCL8, and IL-1RA in the IT group compared with the IV group.
Conclusions
No serious adverse events were reported in the 14 patients with MS treated with T
reg
cells in this |
| doi_str_mv | 10.1007/s40259-020-00462-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2475402028</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2491617192</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1977-71eba50e235a327ee7844dffa35440a926f0b598786d62678d0f7b7d6779764d3</originalsourceid><addsrcrecordid>eNp9kcFqGzEQhpfQQtwkL9CTIJdAUDrSajWr3Mw6SQsJDXYCvQnZq7Vl1itX2oWavkDPecQ8SZU4EOihpxmG7_-ZmT_LPjO4YAD4JQrghaLAgQIIySkeZCPGUFGm4MeH1z6nZQniMPsU4xoAZK5wlP0e1xvXudgH0zvfEd-QaiLOqwkvVm65qiaM4_Ofp2v_6z4_J1O7HFrT-7AjD6SybRtJ40Mat2YbXbekU7txfZ86cje0vdu2lswWrQ0-unhJxuR-ZaIljMz6od4dZx8b00Z78laPssfrq4fqK739fvOtGt_SBVOIFJmdmwIszwuTc7QWSyHqpjF5IQQYxWUD80KVWMpacollDQ3OsZaICqWo86PsbO-7Df7nYGOvNy4u0vams36Imgss0v-Alwk9_Qdd-yF0abtEKSYZMsUTxffUIh0Wg230NriNCTvNQL_kofd56GSqX_PQmET5XhQT3C1teLf-j-ovBGmLuQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2491617192</pqid></control><display><type>article</type><title>Administration of CD4+CD25highCD127−FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study</title><source>SpringerLink Journals - AutoHoldings</source><creator>Chwojnicki, Kamil ; Iwaszkiewicz-Grześ, Dorota ; Jankowska, Anna ; Zieliński, Maciej ; Łowiec, Paweł ; Gliwiński, Mateusz ; Grzywińska, Małgorzata ; Kowalczyk, Kamil ; Konarzewska, Aleksandra ; Glasner, Paulina ; Sakowska, Justyna ; Kulczycka, Julia ; Jaźwińska-Curyłło, Anna ; Kubach, Marlena ; Karaszewski, Bartosz ; Nyka, Walenty ; Szurowska, Edyta ; Trzonkowski, Piotr</creator><creatorcontrib>Chwojnicki, Kamil ; Iwaszkiewicz-Grześ, Dorota ; Jankowska, Anna ; Zieliński, Maciej ; Łowiec, Paweł ; Gliwiński, Mateusz ; Grzywińska, Małgorzata ; Kowalczyk, Kamil ; Konarzewska, Aleksandra ; Glasner, Paulina ; Sakowska, Justyna ; Kulczycka, Julia ; Jaźwińska-Curyłło, Anna ; Kubach, Marlena ; Karaszewski, Bartosz ; Nyka, Walenty ; Szurowska, Edyta ; Trzonkowski, Piotr</creatorcontrib><description>Background
Multiple sclerosis (MS) is an immune-mediated disease in which autoimmune T conventional (T
conv
) cells break the blood–brain barrier and destroy neurons of the central nervous system. It is hypothesized that CD4
+
CD25
high
CD127
−
FoxP3
+
T regulatory (T
reg
) cells may inhibit this destruction through suppressive activity exerted on T
conv
cells.
Methods
We present the results of a phase 1b/2a, open-label, two-arm clinical trial in 14 patients treated with autologous T
reg
cells for relapsing-remitting MS. The patients received either expanded ex vivo T
reg
cells intravenously (intravenous [IV] group,
n
= 11; dose 40 × 10
6
T
reg
cells/kg of body weight) or freshly isolated T
reg
cells intrathecally (intrathecal [IT] group,
n
= 3; dose 1.0 × 10
6
T
reg
cells). Importantly, patients were not treated with any other disease-modifying drugs for at least 6 months before the recruitment and during the follow-up.
Results
No severe adverse events were observed. Self-assessed quality of life (EuroQol–5 Dimensions [EQ-5D] form) did not change and did not differ significantly between the groups. A total of 12 relapses were noted in five intravenously treated patients, who had from one to three attacks per year. Three out of ten participants who completed the trial in the IV group deteriorated more than 1 point on the Expanded Disability Status Scale (EDSS) during the follow-up. At the same time, no patients in the IT group experienced a relapse or such a deterioration in the EDSS. No significant differences were found in the Multiple Sclerosis Functional Composite (MSFC) scale in both the IV and IT groups. Magnetic resonance imaging (MRI) scans revealed a significantly lower change in the T2 lesion volume in the IT group compared to the IV group. The increase in the number of new T2 lesions during the follow-up was significant for the IV group only. There were no significant changes in the level of T
reg
cells or T
conv
cells in the peripheral blood throughout the follow-up or between the groups. Interestingly, T
reg
cells in all patients consisted of two different phenotypes: peripheral T
reg
cells Helios(−) (≈ 20%) and thymic T
reg
cells Helios(+) (≈ 80%). The analysis of the cytokine pattern revealed higher levels of transforming growth factor-α and proinflammatory factors MCP3, CXCL8, and IL-1RA in the IT group compared with the IV group.
Conclusions
No serious adverse events were reported in the 14 patients with MS treated with T
reg
cells in this study. The results suggest that IT administration is more promising than IV administration. Because of the low number of patients recruited, the statistical results may be underpowered and further studies are necessary to reach conclusions on efficacy and safety.
Trial registration
EudraCT: 2014-004320-22; registered 18 November 2014.</description><identifier>ISSN: 1173-8804</identifier><identifier>EISSN: 1179-190X</identifier><identifier>DOI: 10.1007/s40259-020-00462-7</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adverse events ; Antibodies ; Biomedical and Life Sciences ; Biomedicine ; Blood-brain barrier ; Body weight ; Cancer Research ; CD25 antigen ; CD4 antigen ; Central nervous system ; Clinical trials ; Drug dosages ; Foxp3 protein ; Immune system ; Immunoregulation ; Immunosuppressive agents ; Inflammation ; Interleukin 1 receptor antagonist ; Interleukin 1 receptors ; Intravenous administration ; Lymphocytes T ; Magnetic resonance imaging ; Molecular Medicine ; Multiple sclerosis ; Nervous system ; Neurodegeneration ; Neuroimaging ; Original Research Article ; Peripheral blood ; Pharmacotherapy ; Phenotypes ; Quality of life ; Thymus</subject><ispartof>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy, 2021, Vol.35 (1), p.47-60</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2020</rights><rights>Copyright Springer Nature B.V. Jan 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1977-71eba50e235a327ee7844dffa35440a926f0b598786d62678d0f7b7d6779764d3</citedby><cites>FETCH-LOGICAL-c1977-71eba50e235a327ee7844dffa35440a926f0b598786d62678d0f7b7d6779764d3</cites><orcidid>0000-0001-5287-5210</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40259-020-00462-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40259-020-00462-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Chwojnicki, Kamil</creatorcontrib><creatorcontrib>Iwaszkiewicz-Grześ, Dorota</creatorcontrib><creatorcontrib>Jankowska, Anna</creatorcontrib><creatorcontrib>Zieliński, Maciej</creatorcontrib><creatorcontrib>Łowiec, Paweł</creatorcontrib><creatorcontrib>Gliwiński, Mateusz</creatorcontrib><creatorcontrib>Grzywińska, Małgorzata</creatorcontrib><creatorcontrib>Kowalczyk, Kamil</creatorcontrib><creatorcontrib>Konarzewska, Aleksandra</creatorcontrib><creatorcontrib>Glasner, Paulina</creatorcontrib><creatorcontrib>Sakowska, Justyna</creatorcontrib><creatorcontrib>Kulczycka, Julia</creatorcontrib><creatorcontrib>Jaźwińska-Curyłło, Anna</creatorcontrib><creatorcontrib>Kubach, Marlena</creatorcontrib><creatorcontrib>Karaszewski, Bartosz</creatorcontrib><creatorcontrib>Nyka, Walenty</creatorcontrib><creatorcontrib>Szurowska, Edyta</creatorcontrib><creatorcontrib>Trzonkowski, Piotr</creatorcontrib><title>Administration of CD4+CD25highCD127−FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study</title><title>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy</title><addtitle>BioDrugs</addtitle><description>Background
Multiple sclerosis (MS) is an immune-mediated disease in which autoimmune T conventional (T
conv
) cells break the blood–brain barrier and destroy neurons of the central nervous system. It is hypothesized that CD4
+
CD25
high
CD127
−
FoxP3
+
T regulatory (T
reg
) cells may inhibit this destruction through suppressive activity exerted on T
conv
cells.
Methods
We present the results of a phase 1b/2a, open-label, two-arm clinical trial in 14 patients treated with autologous T
reg
cells for relapsing-remitting MS. The patients received either expanded ex vivo T
reg
cells intravenously (intravenous [IV] group,
n
= 11; dose 40 × 10
6
T
reg
cells/kg of body weight) or freshly isolated T
reg
cells intrathecally (intrathecal [IT] group,
n
= 3; dose 1.0 × 10
6
T
reg
cells). Importantly, patients were not treated with any other disease-modifying drugs for at least 6 months before the recruitment and during the follow-up.
Results
No severe adverse events were observed. Self-assessed quality of life (EuroQol–5 Dimensions [EQ-5D] form) did not change and did not differ significantly between the groups. A total of 12 relapses were noted in five intravenously treated patients, who had from one to three attacks per year. Three out of ten participants who completed the trial in the IV group deteriorated more than 1 point on the Expanded Disability Status Scale (EDSS) during the follow-up. At the same time, no patients in the IT group experienced a relapse or such a deterioration in the EDSS. No significant differences were found in the Multiple Sclerosis Functional Composite (MSFC) scale in both the IV and IT groups. Magnetic resonance imaging (MRI) scans revealed a significantly lower change in the T2 lesion volume in the IT group compared to the IV group. The increase in the number of new T2 lesions during the follow-up was significant for the IV group only. There were no significant changes in the level of T
reg
cells or T
conv
cells in the peripheral blood throughout the follow-up or between the groups. Interestingly, T
reg
cells in all patients consisted of two different phenotypes: peripheral T
reg
cells Helios(−) (≈ 20%) and thymic T
reg
cells Helios(+) (≈ 80%). The analysis of the cytokine pattern revealed higher levels of transforming growth factor-α and proinflammatory factors MCP3, CXCL8, and IL-1RA in the IT group compared with the IV group.
Conclusions
No serious adverse events were reported in the 14 patients with MS treated with T
reg
cells in this study. The results suggest that IT administration is more promising than IV administration. Because of the low number of patients recruited, the statistical results may be underpowered and further studies are necessary to reach conclusions on efficacy and safety.
Trial registration
EudraCT: 2014-004320-22; registered 18 November 2014.</description><subject>Adverse events</subject><subject>Antibodies</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood-brain barrier</subject><subject>Body weight</subject><subject>Cancer Research</subject><subject>CD25 antigen</subject><subject>CD4 antigen</subject><subject>Central nervous system</subject><subject>Clinical trials</subject><subject>Drug dosages</subject><subject>Foxp3 protein</subject><subject>Immune system</subject><subject>Immunoregulation</subject><subject>Immunosuppressive agents</subject><subject>Inflammation</subject><subject>Interleukin 1 receptor antagonist</subject><subject>Interleukin 1 receptors</subject><subject>Intravenous administration</subject><subject>Lymphocytes T</subject><subject>Magnetic resonance imaging</subject><subject>Molecular Medicine</subject><subject>Multiple sclerosis</subject><subject>Nervous system</subject><subject>Neurodegeneration</subject><subject>Neuroimaging</subject><subject>Original Research Article</subject><subject>Peripheral blood</subject><subject>Pharmacotherapy</subject><subject>Phenotypes</subject><subject>Quality of life</subject><subject>Thymus</subject><issn>1173-8804</issn><issn>1179-190X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp9kcFqGzEQhpfQQtwkL9CTIJdAUDrSajWr3Mw6SQsJDXYCvQnZq7Vl1itX2oWavkDPecQ8SZU4EOihpxmG7_-ZmT_LPjO4YAD4JQrghaLAgQIIySkeZCPGUFGm4MeH1z6nZQniMPsU4xoAZK5wlP0e1xvXudgH0zvfEd-QaiLOqwkvVm65qiaM4_Ofp2v_6z4_J1O7HFrT-7AjD6SybRtJ40Mat2YbXbekU7txfZ86cje0vdu2lswWrQ0-unhJxuR-ZaIljMz6od4dZx8b00Z78laPssfrq4fqK739fvOtGt_SBVOIFJmdmwIszwuTc7QWSyHqpjF5IQQYxWUD80KVWMpacollDQ3OsZaICqWo86PsbO-7Df7nYGOvNy4u0vams36Imgss0v-Alwk9_Qdd-yF0abtEKSYZMsUTxffUIh0Wg230NriNCTvNQL_kofd56GSqX_PQmET5XhQT3C1teLf-j-ovBGmLuQ</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Chwojnicki, Kamil</creator><creator>Iwaszkiewicz-Grześ, Dorota</creator><creator>Jankowska, Anna</creator><creator>Zieliński, Maciej</creator><creator>Łowiec, Paweł</creator><creator>Gliwiński, Mateusz</creator><creator>Grzywińska, Małgorzata</creator><creator>Kowalczyk, Kamil</creator><creator>Konarzewska, Aleksandra</creator><creator>Glasner, Paulina</creator><creator>Sakowska, Justyna</creator><creator>Kulczycka, Julia</creator><creator>Jaźwińska-Curyłło, Anna</creator><creator>Kubach, Marlena</creator><creator>Karaszewski, Bartosz</creator><creator>Nyka, Walenty</creator><creator>Szurowska, Edyta</creator><creator>Trzonkowski, Piotr</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5287-5210</orcidid></search><sort><creationdate>2021</creationdate><title>Administration of CD4+CD25highCD127−FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study</title><author>Chwojnicki, Kamil ; Iwaszkiewicz-Grześ, Dorota ; Jankowska, Anna ; Zieliński, Maciej ; Łowiec, Paweł ; Gliwiński, Mateusz ; Grzywińska, Małgorzata ; Kowalczyk, Kamil ; Konarzewska, Aleksandra ; Glasner, Paulina ; Sakowska, Justyna ; Kulczycka, Julia ; Jaźwińska-Curyłło, Anna ; Kubach, Marlena ; Karaszewski, Bartosz ; Nyka, Walenty ; Szurowska, Edyta ; Trzonkowski, Piotr</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1977-71eba50e235a327ee7844dffa35440a926f0b598786d62678d0f7b7d6779764d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adverse events</topic><topic>Antibodies</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood-brain barrier</topic><topic>Body weight</topic><topic>Cancer Research</topic><topic>CD25 antigen</topic><topic>CD4 antigen</topic><topic>Central nervous system</topic><topic>Clinical trials</topic><topic>Drug dosages</topic><topic>Foxp3 protein</topic><topic>Immune system</topic><topic>Immunoregulation</topic><topic>Immunosuppressive agents</topic><topic>Inflammation</topic><topic>Interleukin 1 receptor antagonist</topic><topic>Interleukin 1 receptors</topic><topic>Intravenous administration</topic><topic>Lymphocytes T</topic><topic>Magnetic resonance imaging</topic><topic>Molecular Medicine</topic><topic>Multiple sclerosis</topic><topic>Nervous system</topic><topic>Neurodegeneration</topic><topic>Neuroimaging</topic><topic>Original Research Article</topic><topic>Peripheral blood</topic><topic>Pharmacotherapy</topic><topic>Phenotypes</topic><topic>Quality of life</topic><topic>Thymus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chwojnicki, Kamil</creatorcontrib><creatorcontrib>Iwaszkiewicz-Grześ, Dorota</creatorcontrib><creatorcontrib>Jankowska, Anna</creatorcontrib><creatorcontrib>Zieliński, Maciej</creatorcontrib><creatorcontrib>Łowiec, Paweł</creatorcontrib><creatorcontrib>Gliwiński, Mateusz</creatorcontrib><creatorcontrib>Grzywińska, Małgorzata</creatorcontrib><creatorcontrib>Kowalczyk, Kamil</creatorcontrib><creatorcontrib>Konarzewska, Aleksandra</creatorcontrib><creatorcontrib>Glasner, Paulina</creatorcontrib><creatorcontrib>Sakowska, Justyna</creatorcontrib><creatorcontrib>Kulczycka, Julia</creatorcontrib><creatorcontrib>Jaźwińska-Curyłło, Anna</creatorcontrib><creatorcontrib>Kubach, Marlena</creatorcontrib><creatorcontrib>Karaszewski, Bartosz</creatorcontrib><creatorcontrib>Nyka, Walenty</creatorcontrib><creatorcontrib>Szurowska, Edyta</creatorcontrib><creatorcontrib>Trzonkowski, Piotr</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chwojnicki, Kamil</au><au>Iwaszkiewicz-Grześ, Dorota</au><au>Jankowska, Anna</au><au>Zieliński, Maciej</au><au>Łowiec, Paweł</au><au>Gliwiński, Mateusz</au><au>Grzywińska, Małgorzata</au><au>Kowalczyk, Kamil</au><au>Konarzewska, Aleksandra</au><au>Glasner, Paulina</au><au>Sakowska, Justyna</au><au>Kulczycka, Julia</au><au>Jaźwińska-Curyłło, Anna</au><au>Kubach, Marlena</au><au>Karaszewski, Bartosz</au><au>Nyka, Walenty</au><au>Szurowska, Edyta</au><au>Trzonkowski, Piotr</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Administration of CD4+CD25highCD127−FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study</atitle><jtitle>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy</jtitle><stitle>BioDrugs</stitle><date>2021</date><risdate>2021</risdate><volume>35</volume><issue>1</issue><spage>47</spage><epage>60</epage><pages>47-60</pages><issn>1173-8804</issn><eissn>1179-190X</eissn><abstract>Background
Multiple sclerosis (MS) is an immune-mediated disease in which autoimmune T conventional (T
conv
) cells break the blood–brain barrier and destroy neurons of the central nervous system. It is hypothesized that CD4
+
CD25
high
CD127
−
FoxP3
+
T regulatory (T
reg
) cells may inhibit this destruction through suppressive activity exerted on T
conv
cells.
Methods
We present the results of a phase 1b/2a, open-label, two-arm clinical trial in 14 patients treated with autologous T
reg
cells for relapsing-remitting MS. The patients received either expanded ex vivo T
reg
cells intravenously (intravenous [IV] group,
n
= 11; dose 40 × 10
6
T
reg
cells/kg of body weight) or freshly isolated T
reg
cells intrathecally (intrathecal [IT] group,
n
= 3; dose 1.0 × 10
6
T
reg
cells). Importantly, patients were not treated with any other disease-modifying drugs for at least 6 months before the recruitment and during the follow-up.
Results
No severe adverse events were observed. Self-assessed quality of life (EuroQol–5 Dimensions [EQ-5D] form) did not change and did not differ significantly between the groups. A total of 12 relapses were noted in five intravenously treated patients, who had from one to three attacks per year. Three out of ten participants who completed the trial in the IV group deteriorated more than 1 point on the Expanded Disability Status Scale (EDSS) during the follow-up. At the same time, no patients in the IT group experienced a relapse or such a deterioration in the EDSS. No significant differences were found in the Multiple Sclerosis Functional Composite (MSFC) scale in both the IV and IT groups. Magnetic resonance imaging (MRI) scans revealed a significantly lower change in the T2 lesion volume in the IT group compared to the IV group. The increase in the number of new T2 lesions during the follow-up was significant for the IV group only. There were no significant changes in the level of T
reg
cells or T
conv
cells in the peripheral blood throughout the follow-up or between the groups. Interestingly, T
reg
cells in all patients consisted of two different phenotypes: peripheral T
reg
cells Helios(−) (≈ 20%) and thymic T
reg
cells Helios(+) (≈ 80%). The analysis of the cytokine pattern revealed higher levels of transforming growth factor-α and proinflammatory factors MCP3, CXCL8, and IL-1RA in the IT group compared with the IV group.
Conclusions
No serious adverse events were reported in the 14 patients with MS treated with T
reg
cells in this study. The results suggest that IT administration is more promising than IV administration. Because of the low number of patients recruited, the statistical results may be underpowered and further studies are necessary to reach conclusions on efficacy and safety.
Trial registration
EudraCT: 2014-004320-22; registered 18 November 2014.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><doi>10.1007/s40259-020-00462-7</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-5287-5210</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1173-8804 |
| ispartof | BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy, 2021, Vol.35 (1), p.47-60 |
| issn | 1173-8804 1179-190X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2475402028 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Adverse events Antibodies Biomedical and Life Sciences Biomedicine Blood-brain barrier Body weight Cancer Research CD25 antigen CD4 antigen Central nervous system Clinical trials Drug dosages Foxp3 protein Immune system Immunoregulation Immunosuppressive agents Inflammation Interleukin 1 receptor antagonist Interleukin 1 receptors Intravenous administration Lymphocytes T Magnetic resonance imaging Molecular Medicine Multiple sclerosis Nervous system Neurodegeneration Neuroimaging Original Research Article Peripheral blood Pharmacotherapy Phenotypes Quality of life Thymus |
| title | Administration of CD4+CD25highCD127−FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T20%3A46%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Administration%20of%20CD4+CD25highCD127%E2%88%92FoxP3+%20Regulatory%20T%20Cells%20for%20Relapsing-Remitting%20Multiple%20Sclerosis:%20A%20Phase%201%20Study&rft.jtitle=BioDrugs%20:%20clinical%20immunotherapeutics,%20biopharmaceuticals,%20and%20gene%20therapy&rft.au=Chwojnicki,%20Kamil&rft.date=2021&rft.volume=35&rft.issue=1&rft.spage=47&rft.epage=60&rft.pages=47-60&rft.issn=1173-8804&rft.eissn=1179-190X&rft_id=info:doi/10.1007/s40259-020-00462-7&rft_dat=%3Cproquest_cross%3E2491617192%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2491617192&rft_id=info:pmid/&rfr_iscdi=true |