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ID 117337
Author
Taylor, Jennie W. University of California, San Francisco
Nejo, Takahide University of California, San Francisco
Gibson, David University of California, San Francisco
Watchmaker, Payal B. University of California, San Francisco
Okada, Kaori University of California, San Francisco
Saijo, Atsuro University of California, San Francisco|Tokushima University KAKEN Search Researchers
Tedesco, Meghan R. University of California, San Francisco
Shai, Anny University of California, San Francisco
Wong, Cynthia M. University of California, San Francisco
Rabbitt, Jane E. University of California, San Francisco
Olin, Michael R. University of Minnesota
Moertel, Christopher L. University of Minnesota
Salazar, Andres M. Oncovir
Molinaro, Annette M. University of California, San Francisco
Phillips, Joanna J. University of California, San Francisco
Butowski, Nicholas A. University of California, San Francisco
Clarke, Jennifer L. University of California, San Francisco
Oberheim Bush, Nancy Ann University of California, San Francisco
Hervey-Jumper, Shawn L. University of California, San Francisco
Theodosopoulos, Philip University of California, San Francisco
Chang, Susan M. University of California, San Francisco
Berger, Mitchel S. University of California, San Francisco
Okada, Hideho University of California, San Francisco|Parker Institute for Cancer Immunotherapy
Content Type
Journal Article
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.
Journal Title
Journal of Clinical Investigation
ISSN
00219738
15588238
NCID
AA00695520
AA12034468
Publisher
American Society for Clinical Investigation
Volume
132
Issue
3
Start Page
e151239
Published Date
2022-02-01
Rights
This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
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departments
Medical Sciences