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

J Gene Med. 2007 Jul;9(7):547-60. doi: 10.1002/jgm.1051.


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-gamma (IFN-gamma) 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-gamma 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-gamma 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Follow-Up Studies
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interferon-gamma / therapeutic use*
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-2 / therapeutic use*
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins / metabolism
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / drug therapy*
  • Retroviridae / genetics*
  • T-Lymphocytes / immunology
  • Transduction, Genetic*
  • Treatment Outcome
  • Vaccination


  • Cancer Vaccines
  • Interleukin-2
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Interferon-gamma
  • Prostate-Specific Antigen