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Phase I/II clinical trial of a Wilms’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer

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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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Acknowledgements

None.

Funding

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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Author notes

  1. Wen Zhang, Xu Lu and Peilin Cui have contributed equally to this study.

Authors and Affiliations

  1. Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 South Lane, Panjiayuan, Chaoyang District, Beijing, 100021, China

    Wen Zhang & Lin Yang

  2. Department of Oncology, Beijing Biohealthcare Biotechnology Co.,Ltd, FL2, Building 3, Park B, Shunyi District Airport High Tech Zoon, Beijing, 101300, China

    Xu Lu, Xuesong Liu, Yue Wang, Xuan Wu & Jingwei Liu

  3. Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

    Peilin Cui

  4. Department of Oncology, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing, 100029, China

    Chunmei Piao

  5. Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, 571199, China

    Man Xiao

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  1. Wen Zhang
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  2. Xu Lu
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Contributions

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.

Corresponding authors

Correspondence to Jingwei Liu or Lin Yang.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

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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Written informed consent was acquired from each patient in the study.

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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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