Allogeneic retrovirally transduced, IL-2- and IFN-γ-secreting cancer cell vaccine in patients with hormone refractory prostate cancer - A phase I clinical trial

Thomas H. Brill, H. R. Kübler, H. V. Randenborgh, F. Fend, H. Pohla, J. Breul, R. Hartung, R. Paul, D. J. Schendel, B. Gansbacher

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background: The purpose of this vaccine study was to determine the safety and feasibility of vaccination with an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant interleukin-2 (IL-2) and interferon-γ (IFN-γ) and to evaluate the efficacy of inducing tumor-specific immune responses in HLA-A2-matched patients with hormone refractory prostate cancer (HRPC). Methods: In a dose-escalating phase I study, HLA-A2-matched HRPC patients received four vaccinations of irradiated allogeneic LNCaP cells retrovirally transduced to secrete IL-2 and IFN-γ at study day 1, 15, 29 and 92 and subsequently every 91 days unless tumor progression was evident. Results: Three patients receiving the first dose level (7.5 million cells) showed no evidence of dose-limiting toxicity or vaccine-related adverse events including autoimmunity. One of three patients receiving the second dose level (15 million cells) developed a transient self-limiting grade 3 local injection site reaction (ulceration) after the eighth vaccination. Vaccine-induced immune responses against a broad array of prostate tumor associated antigens were detected in all six patients. Two of the three patients receiving the higher dose showed a decline in serum prostate-specific antigen (PSA) values of more than 50%, with one patient remaining on protocol for 3 years. Conclusions: Immunisation with the allogeneic LNCaP/IL-2/IFN-γ vaccine is safe and feasible without any dose-limiting toxicity or autoimmunity. A 50% PSA decline was achieved in two of the six patients. This encouraging data provides the scientific rationale for further investigation of the vaccine in a phase II trial.

Original languageEnglish
Pages (from-to)547-560
Number of pages14
JournalJournal of Gene Medicine
Volume9
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

Keywords

  • Cancer immunotherapy
  • Gene therapy
  • IFN-
  • IL-2
  • Prostate cancer
  • Tumor cell vaccine

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