Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas
BACKGROUND: Long-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Clinical Investigation
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803342/ https://www.ncbi.nlm.nih.gov/pubmed/34882581 http://dx.doi.org/10.1172/JCI151239 |
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author | Ogino, Hirokazu Taylor, Jennie W. Nejo, Takahide Gibson, David Watchmaker, Payal B. Okada, Kaori Saijo, Atsuro Tedesco, Meghan R. Shai, Anny Wong, Cynthia M. Rabbitt, Jane E. Olin, Michael R. Moertel, Christopher L. Nishioka, Yasuhiko Salazar, Andres M. Molinaro, Annette M. Phillips, Joanna J. Butowski, Nicholas A. Clarke, Jennifer L. Oberheim Bush, Nancy Ann Hervey-Jumper, Shawn L. Theodosopoulos, Philip Chang, Susan M. Berger, Mitchel S. Okada, Hideho |
author_facet | Ogino, Hirokazu Taylor, Jennie W. Nejo, Takahide Gibson, David Watchmaker, Payal B. Okada, Kaori Saijo, Atsuro Tedesco, Meghan R. Shai, Anny Wong, Cynthia M. Rabbitt, Jane E. Olin, Michael R. Moertel, Christopher L. Nishioka, Yasuhiko Salazar, Andres M. Molinaro, Annette M. Phillips, Joanna J. Butowski, Nicholas A. Clarke, Jennifer L. Oberheim Bush, Nancy Ann Hervey-Jumper, Shawn L. Theodosopoulos, Philip Chang, Susan M. Berger, Mitchel S. Okada, Hideho |
author_sort | Ogino, Hirokazu |
collection | PubMed |
description | BACKGROUND: Long-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy. METHODS: We conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor. RESULTS: A total of 17 eligible patients were enrolled — 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8(+) T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8(+) T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident–like CD8(+) T cells with effector memory phenotype in the TME after the neoadjuvant vaccination. CONCLUSION: The regimen induced effector CD8(+) T cell response in peripheral blood and enabled vaccine-reactive CD8(+) T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02549833. FUNDING: NIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science. |
format | Online Article Text |
id | pubmed-8803342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-88033422022-02-04 Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas Ogino, Hirokazu Taylor, Jennie W. Nejo, Takahide Gibson, David Watchmaker, Payal B. Okada, Kaori Saijo, Atsuro Tedesco, Meghan R. Shai, Anny Wong, Cynthia M. Rabbitt, Jane E. Olin, Michael R. Moertel, Christopher L. Nishioka, Yasuhiko Salazar, Andres M. Molinaro, Annette M. Phillips, Joanna J. Butowski, Nicholas A. Clarke, Jennifer L. Oberheim Bush, Nancy Ann Hervey-Jumper, Shawn L. Theodosopoulos, Philip Chang, Susan M. Berger, Mitchel S. Okada, Hideho J Clin Invest Clinical Medicine BACKGROUND: Long-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy. METHODS: We conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor. RESULTS: A total of 17 eligible patients were enrolled — 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8(+) T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8(+) T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident–like CD8(+) T cells with effector memory phenotype in the TME after the neoadjuvant vaccination. CONCLUSION: The regimen induced effector CD8(+) T cell response in peripheral blood and enabled vaccine-reactive CD8(+) T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02549833. FUNDING: NIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science. American Society for Clinical Investigation 2022-02-01 2022-02-01 /pmc/articles/PMC8803342/ /pubmed/34882581 http://dx.doi.org/10.1172/JCI151239 Text en © 2022 Ogino et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Clinical Medicine Ogino, Hirokazu Taylor, Jennie W. Nejo, Takahide Gibson, David Watchmaker, Payal B. Okada, Kaori Saijo, Atsuro Tedesco, Meghan R. Shai, Anny Wong, Cynthia M. Rabbitt, Jane E. Olin, Michael R. Moertel, Christopher L. Nishioka, Yasuhiko Salazar, Andres M. Molinaro, Annette M. Phillips, Joanna J. Butowski, Nicholas A. Clarke, Jennifer L. Oberheim Bush, Nancy Ann Hervey-Jumper, Shawn L. Theodosopoulos, Philip Chang, Susan M. Berger, Mitchel S. Okada, Hideho Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas |
title | Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas |
title_full | Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas |
title_fullStr | Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas |
title_full_unstemmed | Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas |
title_short | Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas |
title_sort | randomized trial of neoadjuvant vaccination with tumor-cell lysate induces t cell response in low-grade gliomas |
topic | Clinical Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803342/ https://www.ncbi.nlm.nih.gov/pubmed/34882581 http://dx.doi.org/10.1172/JCI151239 |
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