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Cancer Immunol Immunother. 2018 Oct 10. doi: 10.1007/s00262-018-2257-2. [Epub ahead of print]

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

Author information

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.
2
Department of Oncology, Beijing Biohealthcare Biotechnology Co.,Ltd, FL2, Building 3, Park B, Shunyi District Airport High Tech Zoon, Beijing, 101300, China.
3
Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
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.
5
Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, 571199, China.
6
Department of Oncology, Beijing Biohealthcare Biotechnology Co.,Ltd, FL2, Building 3, Park B, Shunyi District Airport High Tech Zoon, Beijing, 101300, China. ljwgirl361@163.com.
7
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. 403182179@qq.com.

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:

Cytotoxic T lymphocytes; Dendritic cell; Immunotherapy; Tumor-associated antigens; WT1

PMID:
30306202
DOI:
10.1007/s00262-018-2257-2

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