Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas

Hirokazu Ogino, Jennie W. Taylor, Takahide Nejo, David Gibson, Payal B. Watchmaker, Kaori Okada, Atsuro Saijo, Meghan R. Tedesco, Anny Shai, Cynthia M. Wong, Jane E. Rabbitt, Michael R. Olin, Christopher L. Moertel, Yasuhiko Nishioka, Andres M. Salazar, Annette M. Molinaro, Joanna J. Phillips, Nicholas A. Butowski, Jennifer L. Clarke, Nancy Ann Oberheim BushShawn L. Hervey-Jumper, Philip Theodosopoulos, Susan M. Chang, Mitchel S. Berger, Hideho Okada

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number151239
JournalJournal of Clinical Investigation
Volume132
Issue number3
DOIs
StatePublished - Feb 1 2022

Bibliographical note

Funding Information:
The authors thank the following individuals and organizations: the study participants and their families; all staff of the Department of Neurological Surgery and Division of Neuro-Oncology at UCSF for their assistance, advice, and helpful discussions; David McKenna Jr. (Department of Pediatrics at University of Minnesota School of Medicine) for preparation and distribution of the vaccine; Lawrence Fong and the Cancer Immunotherapy Laboratory at UCSF for the processing and banking of patient-derived peripheral blood samples; the Immune Assessment Core at UCLA for Luminex multiplex assay services; the UCSF Parnassus Flow Cytometry Core for mass cytometry services and use of the CyTOF2 Charmander; the CoLabs at UCSF for preparation of scRNA/TCR-Seq libraries and sequencing; Adaptive Biotechnologies for bulk TCR-Seq services; and the DNA Technologies and Expression Analysis Core at UC Davis Genome Center for tumor bulk RNA-Seq services. This work was supported by NIH grants 1R35NS105068 and 1R21CA233856 (to H. Okada), loglio by Dabbiere Foundation (to H. Okada), Parker Institute for Cancer Immunotherapy (to H. Okada), and a fellowship from Daiichi San-kyo Foundation of Life Science (to H. Ogino). Services were also provided by the UCSF Brain Tumor SPORE Biorepository NIH/ NCI 5P50CA097257-18.

Funding Information:
FUNDING. NIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.

Publisher Copyright:
© 2022, Ogino et al.

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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