Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas
Hirokazu Ogino, … , Mitchel S. Berger, Hideho Okada
Hirokazu Ogino, … , Mitchel S. Berger, Hideho Okada
Published December 9, 2021
Citation Information: J Clin Invest. 2022;132(3):e151239. https://doi.org/10.1172/JCI151239.
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Clinical Medicine Oncology Vaccines

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

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.TRIAL REGISTRATION ClinicalTrials.gov NCT02549833.FUNDING NIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.

Authors

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 Bush, Shawn L. Hervey-Jumper, Philip Theodosopoulos, Susan M. Chang, Mitchel S. Berger, Hideho Okada

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Figure 1

Study schema.

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Study schema. Patients were randomized to arm 1 or 2. Patients in arm 1 ...
Patients were randomized to arm 1 or 2. Patients in arm 1 received GBM6-AD lysate and poly-ICLC on days –23 ± 2, –16 ± 2, –9 ± 2, and –2 relative to the scheduled surgery. At least 2 weeks after the postoperative steroid was tapered, but within 10 weeks after surgery, patients in arm 1 and arm 2 started receiving the GBM6-AD/poly-ICLC vaccines every 3 weeks for 5 doses (weeks A1, A4, A7, A10, and A13; defined as the weeks from first adjuvant vaccine dose) followed by booster vaccines at weeks A32 and A48.