Abstract
Dendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms’ tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with autologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and clinical and immunological responses as the principal endpoints. All of the adverse events to DC vaccinations were tolerable under an adjuvant setting. The clinical response was stable disease in seven patients. Karnofsky Performance Scale scores were enhanced, and computed tomography scans revealed tumor shrinkage in three of seven patients. Human leukocyte antigen (HLA)/WT1-tetramer and cytoplasmic IFN-γ assays were used to examine the induction of a WT-1-specific immune response. The immunological responses to DC vaccination were significantly correlated with fewer myeloid-derived suppressor cells (P = 0.045) in the pretreated peripheral blood. These outcomes offered initial clinical evidence that the WT1 peptide-pulsed DC vaccination is a potential treatment for advanced cancer.
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Abbreviations
- CTLs:
-
Cytotoxic T lymphocytes
- DC:
-
Dendritic cell
- ELISPOT:
-
Enzyme-linked immuno spot
- HIV:
-
Human immunodeficiency virus
- HLA:
-
Human leukocyte antigen
- IFN:
-
Interferon
- KPS:
-
Karnofsky Performance Status
- MDSCs:
-
Myeloid-derived suppressor cells
- PBMCs:
-
Peripheral blood mononuclear cells
- RECIST:
-
Response Evaluation Criteria in Solid Tumors
- TAA:
-
Tumor-associated antigens
- Treg:
-
Regulatory cells
- WT1:
-
Wilms tumor protein 1
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This work was supported by the National Natural Science Foundation of China (81770468), Beijing Municipal Natural Science Foundation (7162030) and the Beijing Science and Technology Plan special issue (Z14010101101).
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WZ, XL and PC designed and coordinated the project. CP, MX, XL, YW and XW performed the clinical and laboratory experiments. All authors take responsibility for the accuracy of the final revision of the text. LY and JL took the lead in writing the paper.
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This trial was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and was registered with the Chinese Clinical Trials Registry (ChiCTR-IPR-15005923).
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Zhang, W., Lu, X., Cui, P. et al. Phase I/II clinical trial of a Wilms’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer. Cancer Immunol Immunother 68, 121–130 (2019). https://doi.org/10.1007/s00262-018-2257-2
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DOI: https://doi.org/10.1007/s00262-018-2257-2