Full-Length Dominant-Negative Survivin for Cancer Immunotherapy

Vladimir Pisarev, Bin Yu, Raoul Salup, Simon Sherman, Dario C. Altieri, Dmitry I. Gabrilovich

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Purpose: The goal of this study is to investigate the possible utility of dendritic cells (DCs) transduced with the human full-length dominant-negative survivin for cancer immunotherapy. Experimental Design: Mononuclear cells were collected from HLA-A2-positive healthy volunteers and patients with prostate cancer. DCs were transduced with an adenoviral vector containing a full-length, dominant-negative survivin gene. After three rounds of stimulation, the T-cell response against three different survivin-derived HLA-A2-matching peptides was tested in IFN-γy enzyme-linked immunospot and CTL assays. Results: Seven of eight healthy volunteers and cancer patients showed a significant response to at least two different survivin-derived epitopes in the enzyme-linked immunospot assay. One patient responded to only one peptide. All four healthy volunteers and two of three patients tested demonstrated a specific CTL response against T2 target cells loaded with one survivin-derived epitope. Two donors and two patients had a significant CTL response against two different epitopes. Significant cytotoxic activity was seen against HLA-A2-positive MCF-7 tumor cells that express survivin. That response was specific for survivin and was MHC class I restricted. Because survivin is expressed in CD34+ hematopoietic progenitor cells (HPCs), we tested whether the antisurvivin CTLs can recognize normal HPCs. The incubation of survivin-specific CTLs with CD34+ cells did not significantly decrease the colony-forming ability of HPCs. Conclusions: DCs transduced with dominant-negative survivin induce potent survivin-specific CTL responses able to recognize and kill tumor cells. This response does not significantly affect HPCs. Thus, this study may provide rationale for immunotherapeutic clinical trials using a DC vaccine transduced with the dominant-negative survivin.

Original languageEnglish (US)
Pages (from-to)6523-6533
Number of pages11
JournalClinical Cancer Research
Volume9
Issue number17
StatePublished - Dec 15 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pisarev, V., Yu, B., Salup, R., Sherman, S., Altieri, D. C., & Gabrilovich, D. I. (2003). Full-Length Dominant-Negative Survivin for Cancer Immunotherapy. Clinical Cancer Research, 9(17), 6523-6533.