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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

  • Wen Zhang
  • Xu Lu
  • Peilin Cui
  • Chunmei Piao
  • Man Xiao
  • Xuesong Liu
  • Yue Wang
  • Xuan Wu
  • Jingwei Liu
  • Lin Yang
Clinical Trial Report
  • 143 Downloads

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.

Keywords

Dendritic cell WT1 Tumor-associated antigens Cytotoxic T lymphocytes Immunotherapy 

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

Notes

Acknowledgements

None.

Author 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.

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).

Compliance with ethical standards

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).

Informed consent

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

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.Department of OncologyBeijing Biohealthcare Biotechnology Co.,LtdBeijingChina
  3. 3.Department of Gastroenterology, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  4. 4.Department of Oncology, Beijing Institute of Heart Lung and Blood Vessel DiseasesBeijing Anzhen Hospital Affiliated to the Capital Medical UniversityBeijingChina
  5. 5.Department of Biochemistry and Molecular BiologyHainan Medical CollegeHaikouChina

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