Cargando…

Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial

Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a...

Descripción completa

Detalles Bibliográficos
Autores principales: Frank, Matthew J., Khodadoust, Michael S., Czerwinski, Debra K., Haabeth, Ole A.W., Chu, Michael P., Miklos, David B., Advani, Ranjana H., Alizadeh, Ash A., Gupta, Neel K., Maeda, Lauren S., Reddy, Sunil A., Laport, Ginna G., Meyer, Everett H., Negrin, Robert S., Rezvani, Andrew R., Weng, Wen-Kai, Sheehan, Kevin, Faham, Malek, Okada, Ami, Moore, A. Holliston, Phillips, Destiny L., Wapnir, Irene L., Brody, Joshua D., Levy, Ronald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478738/
https://www.ncbi.nlm.nih.gov/pubmed/32558897
http://dx.doi.org/10.1084/jem.20191712
_version_ 1783580120511938560
author Frank, Matthew J.
Khodadoust, Michael S.
Czerwinski, Debra K.
Haabeth, Ole A.W.
Chu, Michael P.
Miklos, David B.
Advani, Ranjana H.
Alizadeh, Ash A.
Gupta, Neel K.
Maeda, Lauren S.
Reddy, Sunil A.
Laport, Ginna G.
Meyer, Everett H.
Negrin, Robert S.
Rezvani, Andrew R.
Weng, Wen-Kai
Sheehan, Kevin
Faham, Malek
Okada, Ami
Moore, A. Holliston
Phillips, Destiny L.
Wapnir, Irene L.
Brody, Joshua D.
Levy, Ronald
author_facet Frank, Matthew J.
Khodadoust, Michael S.
Czerwinski, Debra K.
Haabeth, Ole A.W.
Chu, Michael P.
Miklos, David B.
Advani, Ranjana H.
Alizadeh, Ash A.
Gupta, Neel K.
Maeda, Lauren S.
Reddy, Sunil A.
Laport, Ginna G.
Meyer, Everett H.
Negrin, Robert S.
Rezvani, Andrew R.
Weng, Wen-Kai
Sheehan, Kevin
Faham, Malek
Okada, Ami
Moore, A. Holliston
Phillips, Destiny L.
Wapnir, Irene L.
Brody, Joshua D.
Levy, Ronald
author_sort Frank, Matthew J.
collection PubMed
description Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of ≥1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.
format Online
Article
Text
id pubmed-7478738
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-74787382021-03-07 Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial Frank, Matthew J. Khodadoust, Michael S. Czerwinski, Debra K. Haabeth, Ole A.W. Chu, Michael P. Miklos, David B. Advani, Ranjana H. Alizadeh, Ash A. Gupta, Neel K. Maeda, Lauren S. Reddy, Sunil A. Laport, Ginna G. Meyer, Everett H. Negrin, Robert S. Rezvani, Andrew R. Weng, Wen-Kai Sheehan, Kevin Faham, Malek Okada, Ami Moore, A. Holliston Phillips, Destiny L. Wapnir, Irene L. Brody, Joshua D. Levy, Ronald J Exp Med Article Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of ≥1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe. Rockefeller University Press 2020-06-19 /pmc/articles/PMC7478738/ /pubmed/32558897 http://dx.doi.org/10.1084/jem.20191712 Text en © 2020 Frank et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Frank, Matthew J.
Khodadoust, Michael S.
Czerwinski, Debra K.
Haabeth, Ole A.W.
Chu, Michael P.
Miklos, David B.
Advani, Ranjana H.
Alizadeh, Ash A.
Gupta, Neel K.
Maeda, Lauren S.
Reddy, Sunil A.
Laport, Ginna G.
Meyer, Everett H.
Negrin, Robert S.
Rezvani, Andrew R.
Weng, Wen-Kai
Sheehan, Kevin
Faham, Malek
Okada, Ami
Moore, A. Holliston
Phillips, Destiny L.
Wapnir, Irene L.
Brody, Joshua D.
Levy, Ronald
Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial
title Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial
title_full Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial
title_fullStr Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial
title_full_unstemmed Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial
title_short Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial
title_sort autologous tumor cell vaccine induces antitumor t cell immune responses in patients with mantle cell lymphoma: a phase i/ii trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478738/
https://www.ncbi.nlm.nih.gov/pubmed/32558897
http://dx.doi.org/10.1084/jem.20191712
work_keys_str_mv AT frankmatthewj autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT khodadoustmichaels autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT czerwinskidebrak autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT haabetholeaw autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT chumichaelp autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT miklosdavidb autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT advaniranjanah autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT alizadehasha autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT guptaneelk autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT maedalaurens autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT reddysunila autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT laportginnag autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT meyereveretth autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT negrinroberts autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT rezvaniandrewr autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT wengwenkai autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT sheehankevin autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT fahammalek autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT okadaami autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT mooreaholliston autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT phillipsdestinyl autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT wapnirirenel autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT brodyjoshuad autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial
AT levyronald autologoustumorcellvaccineinducesantitumortcellimmuneresponsesinpatientswithmantlecelllymphomaaphaseiiitrial