Abstract
Background
Tumor vaccines for hepatocellular carcinoma (HCC) is an area of intense interest. Tremendous clinical trials have been conducted globally, but the efficacy and security of tumor vaccines are elusive. The aim of our study was to evaluate the efficacy and security of tumor vaccines.
Methods
All relevant studies were identified in PubMed, EMBASE, Web of science and Cochrane Library databases. Objective response rate (ORR), median overall survival (OS), or median progression-free survival (PFS) and 95% CI were meta-analyzed based on the random-effects model. The individual-level data of OS, PFS were pooled by conducting survival analysis. All observed adverse events were collected.
Results
31 studies containing 35 eligible cohorts with 932 HCC patients were included. The pooled ORR were 7% (95% CI 3–14%), while ORR of dendritic cell (DC) vaccine (19%, 95% CI 11–29%) were highly significant than ORR of peptide vaccine (1%, 95% CI 0–5%). The pooled median OS and PFS were 13.67 months (95% CI 8.20–22.80) and 6.19 months (95% CI 2.97–12.91), respectively. The pooled median OS (DC vaccine: median OS = 21.77 months, 95% CI 18.33–25.86; Peptide vaccine: median OS = 10.08 months, 95% CI 5.23–19.44) and PFS (DC vaccine: median PFS = 11.01 months, 95% CI 5.25–23.09; Peptide vaccine: median PFS = 1.97 months, 95% CI 1.53–2.54) of DC vaccine were also longer than that of peptide vaccine. HBV-related HCC may acquire more benefits from tumor vaccines than HCV-related HCC. In almost all studies, the observed toxicities were moderate even tiny.
Conclusions
Tumor vaccines for HCC, especially DC vaccine, are safe and worth exploring. More high-quality prospective studies are warranted.
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Data availability
The manuscript's guarantors (C.-L.H. and T.L.) affirm that the manuscript shows an honest, accurate, and transparent study; that no important aspects of the study have been omitted and that any discrepancies from the study have been explained.
Abbreviations
- HCC:
-
Hepatocellular carcinoma
- DC:
-
Dendritic cell
- PRISMA:
-
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
- ORR:
-
Objective response rate
- CI:
-
Confidence intervals
- REM:
-
Random-effect models
- FEM:
-
Fixed-effects model
- PFS:
-
Progression-free survival
- OS:
-
Overall survival
- CBs:
-
Confidence bands
- GM-CSF:
-
Granulocyte macrophage colony-stimulating factor
- TGFβ:
-
Transforming growth factor beta
- FANG:
-
A form of whole tumor vaccine
- CIK:
-
Cytokine-induced killer cells
- CTL:
-
Cytotoxic T lymphocytes
- NK:
-
Natural killer cell
- PD-1:
-
Programmed cell death ligand 1
- CTL4:
-
Cytotoxic T lymphocyte-associated protein 4
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Funding
This work was supported by the grants from the Taishan Scholars Program for Young Expert of Shandong Province (Grant No. tsqn20161064), National Natural Science Foundation of China (Grant No. 82073200 & 81874178), Major Basic Research of Shandong Provincial Natural Science Foundation (Grant No. ZR202105070027), and founds for Independent Cultivation of Innovative Team from Universities in Jinan (Grant No.2020GXRC023).
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All authors had full access to the data in the study and take responsibility for the integrity and authenticity of the data C-LH formulated the study objective, conceptualized the study, performed the statistical analysis, and interpreted the results; Y-CY and L-JY designed the protocol of the systematic reviews; G-XM, C-CY, H L provided important guidance to the protocols and modified them; C-LH and Z-ND respectively evaluated the availability of every study and disagreements were identified and debated with Z-RD J-GH, and Z-QC performed the methodology, data collection, and data validation; C-LH and TL guided the task of formal statistical analysis and analysis of the data; C-LH and TL contributed to outlining the manuscript and drafting the manuscript; C-LH and TL verified the underlying data TL supervised and coordinated the study. All authors have read and approved the final version.
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Han, CL., Yan, YC., Yan, LJ. et al. Efficacy and security of tumor vaccines for hepatocellular carcinoma: a systemic review and meta-analysis of the last 2 decades. J Cancer Res Clin Oncol 149, 1425–1441 (2023). https://doi.org/10.1007/s00432-022-04008-y
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DOI: https://doi.org/10.1007/s00432-022-04008-y