title: Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of prostate cancer.
abstract: Prophylactic vaccination is arguably the most effective medical preventative method. After local inoculation, vaccines induce antigen-specific systemic immunity, protecting the whole body. Systemic antitumour immunity can cure advanced cancer, but will therapeutic vaccination suffice? A vaccine for castration-refractory prostate cancer (CRPC) was approved by regulatory authority, but its evidence is disputed. We critically reviewed the clinical efficacy of therapeutic cancer vaccines for prostate cancer, including the results of 31 clinical studies employing vaccines-only, and another 10 studies combining vaccines with immune co-stimulation. Vaccinations yielded immunological responses, but no study showed evidence for clinically relevant therapeutic improvement. Clinical failure of therapeutic vaccination is discussed in the light of immunological dogmas and mechanisms of antitumour therapies. We propose that cancer immunotherapy might be improved by immunological danger, i.e. disturbing tumour homeostasis by destroying the tumour tissue or inducing local inflammation. Such danger might override immunological tolerance, and thereby allow clinically relevant anticancer results.
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, the Netherlands Paper@johnjljacobs.nl.
authors.forename: John J L
authors.initials: JJ
authors.lastname: Jacobs
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, the Netherlands Department of Internal Medicine, Kennemer Gasthuis Haarlem, the Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: Snackey
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, the Netherlands Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Geldof
authors.affiliation: Faculty of Medicine, Vilnius University, Vilnius, Lithuania Centre for Innovative Medicine, Vilnius, Lithuania.
authors.forename: Dainius
authors.initials: D
authors.lastname: Characiejus
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: R Jeroen A
authors.initials: RJ
authors.lastname: Van Moorselaar
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Den Otter
mesh_terms: D019496:Cancer Vaccines / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D014611:Vaccination / Q000592:standards*
chemical_list: D019496:Cancer Vaccines
keywords: Clinical; cancer; immunotherapy; review; therapeutic vaccination