Autologous adoptive immune-cell therapy elicited a durable response with enhanced immune reaction signatures in patients with recurrent glioblastoma: An open label, phase I/IIa trial

PLoS One. 2021 Mar 10;16(3):e0247293. doi: 10.1371/journal.pone.0247293. eCollection 2021.

Abstract

Glioblastoma multiforme (GBM) is an aggressive malignancy classified by the World Health Organization as a grade IV glioma. Despite the availability of aggressive standard therapies, most patients experience recurrence, for which there are currently no effective treatments. We aimed to conduct a phase I/IIa clinical trial to investigate the safety and efficacy of adoptive, ex-vivo-expanded, and activated natural killer cells and T lymphocytes from peripheral blood mononuclear cells of patients with recurrent GBM. This study was a single-arm, open-label, investigator-initiated trial on 14 patients recruited between 2013 and 2017. The immune cells were administered via intravenous injection 24 times at 2-week intervals after surgical resection or biopsy. The safety and clinical efficacy of this therapy was examined by assessing adverse events and comparing 2-year overall survival (OS). Transcriptomic analysis of tumor tissues was performed using NanoString to identify the mechanism of therapeutic efficacy. No grade 4 or 5 severe adverse events were observed. The most common treatment-related adverse events were grade 1 or 2 in severity. The most severe adverse event was grade 3 fever. Median OS was 22.5 months, and the median progression-free survival was 10 months. Five patients were alive for over 2 years and showed durable response with enhanced immune reaction transcriptomic signatures without clinical decline until the last follow-up after completion of the therapy. In conclusion, autologous adoptive immune-cell therapy was safe and showed durable response in patients with enhanced immune reaction signatures. This therapy may be effective for recurrent GBM patients with high immune response in their tumor microenvironments. Trial registration: The Korea Clinical Research Information Service database: KCT0003815, Registered 18 April 2019, retrospectively registered.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / genetics
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • Female
  • Gene Expression Profiling
  • Glioblastoma / genetics
  • Glioblastoma / immunology
  • Glioblastoma / therapy*
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / therapy*
  • Prospective Studies
  • Survival Analysis
  • Transplantation, Autologous / adverse effects
  • Treatment Outcome

Grant support

This research was supported by grants of Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Korea government (MSIT) (Grant No. 2018R1C1B5086460) and the Industrial Technology Innovation Program through the Ministry of Trade, Industry and Energy (Korea), funded by the Ministry of Trade, Industry and Energy, Republic of Korea (Grant No. 10067378). 1.Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Korea government (MSIT) Award Number: 2018R1C1B5086460 Recipient: Jaejoon Lim Role: Study design, Data collection and analysis, Decision to publish, Preparation of the manuscript 2. The Industrial Technology Innovation Program through the Ministry of Trade, Industry and Energy (Korea), funded by the Ministry of Trade, Industry and Energy, Republic of Korea Award Number: 10067378 Recipient: kyunggi Cho Role: Study design, Data collection and analysis, Decision to publish, Preparation of the manuscript.