title: Therapeutic vaccination with an interleukin-2-interferon-gamma-secreting allogeneic tumor vaccine in patients with progressive castration-resistant prostate cancer: a phase I/II trial.
abstract: Immunotherapy with whole cell cancer vaccines has been tested in various tumor types. This study investigated the safety profile and antitumor activity of an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant human interleukin-2 and human interferon-gamma. Thirty HLA-A*0201-matched patients with progressive, castration-resistant prostate cancer received four intradermal injections on days 1, 15, 29, and 92, and then every 90 days, as long as no tumor progression occurred. Three patients received a dose level of 7.5 million cells, and 27 patients received 15 million cells per injection. The primary study criteria were safety and the difference in prostate-specific antigen doubling time (PSA-DT), determined in the pretreatment phase (before the start of vaccination) and in the trial treatment phase (during vaccination). No dose-limiting or autoimmune toxicity was seen. During vaccination there was a significant prolongation of the PSA-DT compared with the prevaccination period (prolongation from 63 to 114 days; p < 0.01; intention to treat). In addition, results showed a period of PSA stabilization of at least 12 weeks, together with stable bone scans in 12 of 30 patients, and 3 patients sustained a >50% decrease in PSA versus baseline. The median overall survival time from first vaccination was 32 months (mean value, 34 months). Immune monitoring revealed T cell stimulation in the majority of patients. This vaccine strategy was found to be safe and well tolerated and was accompanied by prolongation of PSA-DT. The results of this trial warrant clinical development of this vaccine.
authors: Institut für Experimentelle Onkologie und Therapieforschung, Technische Universität München, Klinikum rechts der Isar, 81675 Munich, Germany. Thomas.Brill@lrz.tum.de
authors: Thomas H
authors: TH
authors: Brill
authors: Hubert R
authors: HR
authors: Kübler
authors: Heike
authors: H
authors: Pohla
authors: Alexander
authors: A
authors: Buchner
authors: Falko
authors: F
authors: Fend
authors: Tibor
authors: T
authors: Schuster
authors: Heiner
authors: H
authors: van Randenborgh
authors: Roger
authors: R
authors: Paul
authors: Tania
authors: T
authors: Kummer
authors: Christian
authors: C
authors: Plank
authors: Bernd
authors: B
authors: Eisele
authors: Jürgen
authors: J
authors: Breul
authors: Rudolf
authors: R
authors: Hartung
authors: Dolores J
authors: DJ
authors: Schendel
authors: Bernd
authors: B
authors: Gansbacher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002369:Castration; D045744:Cell Line, Tumor; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D014611:Vaccination / Q000009:adverse effects
chemical_list: D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D007371:Interferon-gamma