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Background <p>Immunotherapy against gliomas, including Glioblastoma multiform (GBM) as the most lethal type combines innate and adaptive immune responses to strengthen systemic and host-specific immunity. Among various cell-based immunotherapies, activated cell therapies utilize autologous immune cells activated ex vivo—such as lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, and cytotoxic T lymphocytes. Despite challenges, LAK laid the groundwork for further progress in activated killer cell therapies, such as CIK cells. CIK cells with their MHC-independent lytic activity, can be rapidly expanded ex vivo and administered as promising anticancer agents. This systematic review aims to assess CIK and LAK-based immunotherapy in glioma patients, their biological evolutionary path, and to compare these therapies across several parameters.</p> Methods <p>Following the PRISMA guideline, a thorough literature search was implemented using four major online databases up to August 2025. Screening and data extraction was performed by two independent reviewers and the quality assessment was evaluated using the Joanna Briggs Institute critical appraisal tool.</p> Results <p>Out of 930 initial papers, 21 studies including 18 quasi-experimental studies, 2 randomized controlled trials, and 1 cohort were selected. GBM was the predominant glioma subtype. LAKs and CIKs were mostly administered intracavitary and intravenously, respectively. LAK therapy increased survival; however, they presented more complications compared to CIK therapy, attributed to factors such as co-administration of IL-2. Bispecific antibodies were administered alongside LAK cells in two studies, which reported a higher survival rate. Hishi et al. demonstrated that 50% of the patients survived after three years, and 40% were free from recurrence. Studies evaluating CIK therapy demonstrated significant improvements in progression-free survival (PFS) and an increased disease control rate based on MRI findings. Kong et al. showed that PFS rose from 5.4 months in the control group to 8.1 months in the intervention group, while overall survival improved from 16.9 months to 22.5 months. No inflammatory cytokine storm or severe allergic reactions were observed in the CIK therapy groups.</p> Conclusions <p>Both LAK and CIK therapies could be beneficial for glioma patients, with CIK being safer and associated with higher efficacy. Although larger clinical trials are needed to consolidate observed outcomes.</p>

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LAK to CIK continuum in glioma immunotherapy: a systematic review of efficacy and safety outcomes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Sana Hamidi,
  • Soroush Morsali,
  • Parna Ghannadikhosh,
  • Afra Darvishi,
  • Mina Afrashteh Nour,
  • Samaneh Zafarabadi,
  • Mehrab Rahmani,
  • Mohammad Amin Doustvandi,
  • Leili Aghebati-Maleki

摘要

Background

Immunotherapy against gliomas, including Glioblastoma multiform (GBM) as the most lethal type combines innate and adaptive immune responses to strengthen systemic and host-specific immunity. Among various cell-based immunotherapies, activated cell therapies utilize autologous immune cells activated ex vivo—such as lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, and cytotoxic T lymphocytes. Despite challenges, LAK laid the groundwork for further progress in activated killer cell therapies, such as CIK cells. CIK cells with their MHC-independent lytic activity, can be rapidly expanded ex vivo and administered as promising anticancer agents. This systematic review aims to assess CIK and LAK-based immunotherapy in glioma patients, their biological evolutionary path, and to compare these therapies across several parameters.

Methods

Following the PRISMA guideline, a thorough literature search was implemented using four major online databases up to August 2025. Screening and data extraction was performed by two independent reviewers and the quality assessment was evaluated using the Joanna Briggs Institute critical appraisal tool.

Results

Out of 930 initial papers, 21 studies including 18 quasi-experimental studies, 2 randomized controlled trials, and 1 cohort were selected. GBM was the predominant glioma subtype. LAKs and CIKs were mostly administered intracavitary and intravenously, respectively. LAK therapy increased survival; however, they presented more complications compared to CIK therapy, attributed to factors such as co-administration of IL-2. Bispecific antibodies were administered alongside LAK cells in two studies, which reported a higher survival rate. Hishi et al. demonstrated that 50% of the patients survived after three years, and 40% were free from recurrence. Studies evaluating CIK therapy demonstrated significant improvements in progression-free survival (PFS) and an increased disease control rate based on MRI findings. Kong et al. showed that PFS rose from 5.4 months in the control group to 8.1 months in the intervention group, while overall survival improved from 16.9 months to 22.5 months. No inflammatory cytokine storm or severe allergic reactions were observed in the CIK therapy groups.

Conclusions

Both LAK and CIK therapies could be beneficial for glioma patients, with CIK being safer and associated with higher efficacy. Although larger clinical trials are needed to consolidate observed outcomes.