Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study
Background Progression after high-dose melphalan with autologous stem cell transplantation (ASCT) in multiple myeloma (MM) may be due in part to immune dysfunction. Regulatory T (Treg) cells reconstitute rapidly after ASCT and inhibit immune responses against myeloma cells.Methods We performed a ran...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2020-05-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000286.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846172938730995712 |
|---|---|
| author | Justin Kline Yuanyuan Zha Benjamin A Derman Todd M Zimmerman Rebecca Malloy Andrzej Jakubowiak Michael R Bishop |
| author_facet | Justin Kline Yuanyuan Zha Benjamin A Derman Todd M Zimmerman Rebecca Malloy Andrzej Jakubowiak Michael R Bishop |
| author_sort | Justin Kline |
| collection | DOAJ |
| description | Background Progression after high-dose melphalan with autologous stem cell transplantation (ASCT) in multiple myeloma (MM) may be due in part to immune dysfunction. Regulatory T (Treg) cells reconstitute rapidly after ASCT and inhibit immune responses against myeloma cells.Methods We performed a randomized study to evaluate two methods of Treg depletion in patients with MM undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 monoclonal antibody (basiliximab 20 mg IV) was administered on day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. Tregs were depleted from autologous stem cell (ASC) grafts with anti-CD25 microbeads and the CliniMACS device in the ex vivo Treg depletion (EVTRD) arm.Results Fifteen patients were enrolled, five in each arm. The conditioning regimen was melphalan 200 mg/m2. Primary objectives included assessments of efficiency of IVTRD/EVTRD, kinetics of Treg depletion and recovery following ASCT, and safety. EVTRD removed 90% of CD4+CD25+ cells from ASC grafts. IVTRD and EVTRD led to reductions in Treg frequency between days +7 and +90 post-transplant compared with the control (p=0.007 and p<0.001, respectively).Conclusions IVTRD and EVTRD are feasible and significantly reduce and delay Treg recovery post-ASCT for MM, and serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes.Trial registration number NCT01526096. |
| format | Article |
| id | doaj-art-2a71796b0469427e954363ddde265cbb |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-2a71796b0469427e954363ddde265cbb2024-11-08T23:10:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000286Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot studyJustin Kline0Yuanyuan Zha1Benjamin A Derman2Todd M Zimmerman3Rebecca Malloy4Andrzej Jakubowiak5Michael R Bishop6Aff22 grid.170205.10000000419367822The University of Chicago 5841 S. Maryland Ave 60637 Chicago IL USAComprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA1 Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois, USA2 BeiGene, San Mateo, CA, United States1 Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois, USA1 Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois, USA11 The David and Etta Jonas Center for Cellular Therapy, Chicago, Illinois, USABackground Progression after high-dose melphalan with autologous stem cell transplantation (ASCT) in multiple myeloma (MM) may be due in part to immune dysfunction. Regulatory T (Treg) cells reconstitute rapidly after ASCT and inhibit immune responses against myeloma cells.Methods We performed a randomized study to evaluate two methods of Treg depletion in patients with MM undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 monoclonal antibody (basiliximab 20 mg IV) was administered on day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. Tregs were depleted from autologous stem cell (ASC) grafts with anti-CD25 microbeads and the CliniMACS device in the ex vivo Treg depletion (EVTRD) arm.Results Fifteen patients were enrolled, five in each arm. The conditioning regimen was melphalan 200 mg/m2. Primary objectives included assessments of efficiency of IVTRD/EVTRD, kinetics of Treg depletion and recovery following ASCT, and safety. EVTRD removed 90% of CD4+CD25+ cells from ASC grafts. IVTRD and EVTRD led to reductions in Treg frequency between days +7 and +90 post-transplant compared with the control (p=0.007 and p<0.001, respectively).Conclusions IVTRD and EVTRD are feasible and significantly reduce and delay Treg recovery post-ASCT for MM, and serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes.Trial registration number NCT01526096.https://jitc.bmj.com/content/8/1/e000286.full |
| spellingShingle | Justin Kline Yuanyuan Zha Benjamin A Derman Todd M Zimmerman Rebecca Malloy Andrzej Jakubowiak Michael R Bishop Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study Journal for ImmunoTherapy of Cancer |
| title | Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study |
| title_full | Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study |
| title_fullStr | Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study |
| title_full_unstemmed | Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study |
| title_short | Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study |
| title_sort | regulatory t cell depletion in the setting of autologous stem cell transplantation for multiple myeloma pilot study |
| url | https://jitc.bmj.com/content/8/1/e000286.full |
| work_keys_str_mv | AT justinkline regulatorytcelldepletioninthesettingofautologousstemcelltransplantationformultiplemyelomapilotstudy AT yuanyuanzha regulatorytcelldepletioninthesettingofautologousstemcelltransplantationformultiplemyelomapilotstudy AT benjaminaderman regulatorytcelldepletioninthesettingofautologousstemcelltransplantationformultiplemyelomapilotstudy AT toddmzimmerman regulatorytcelldepletioninthesettingofautologousstemcelltransplantationformultiplemyelomapilotstudy AT rebeccamalloy regulatorytcelldepletioninthesettingofautologousstemcelltransplantationformultiplemyelomapilotstudy AT andrzejjakubowiak regulatorytcelldepletioninthesettingofautologousstemcelltransplantationformultiplemyelomapilotstudy AT michaelrbishop regulatorytcelldepletioninthesettingofautologousstemcelltransplantationformultiplemyelomapilotstudy |