5 augustus 2010: de aanpak met dendritische celtherapie bij prostaatkanker blijkt ook uitstekende resultaten te geven op langere termijn zo meldt Northwest Biotherepeutics op hun website. Hun aanpak met dendritische celtherapie (DCVax prostate) geeft betere resultaten dan Provenge zo claimen zij.

The survival data seen to date with the NWBT technology in prostate cancer has been exceptional. While Dendreon’s Provenge has demonstrated a median survival in pivotal trials of 25.9 months, NWBT’s DCVax®-Prostate has demonstrated median survival in Phase I/II studies of 38.7 months, with 64% of patients surviving at three years (Provenge three year survival:
34%). DCVax®-Prostate has been cleared by FDA to begin a US Phase Ill clinical trial.

Een interessante ontwikkeling omdat Northwest Biotherapeutics werkt met een zuivere vorm van dendritische celtherapie zonder andere toegevoegde middelen. Zie ook hieronder onze berichtgeving over DCVax prostate van september 2008.

24 september 2008: Bron: Northwest Biotherapeutics en Universiteit van Freiburg

Immuuntherapie met focus op dendritische celtherapie lijkt een doorbraak te geven in het behandelen van prostaatkanker. Northwest Biotherapeutics initieert een fase III trial met DCVax - prostate nadat blijkt dat uit eerdere fase I en II trials is gebleken dat DCVax - prostate voor significante effectiviteit scoort bij prostaatkankerpatienten zonder uitzaaiingen of met maximaal drie uitzaaiingen. 80% reageert positief op de immuuntherapie en de mediane overlevingstijd is tijdens de studie nu meer dan verdrievoudigd en het eindpunt is nog niet bereikt. Daarnaast heeft de universiteit van Freibrug een meta analyse gepubliceerd van gerandomiseerde studies met verschillende vormen van immuuntherapie. Ook daaruit bljikt dat immuuntherapie bij prostaatkanker een effectieve manier van behandelen is waarbij opvalt dat vooral de dendritische celtherapie goed scoort wat effectiveit en prognoses in verbetering van aanpak betreft. Hier achtereenvolgens het abstract van de fase I/II studie met DCVax - prostate en daaronder het abstract en conclusie van de meta analyse studie van de universiteit van Freiburg. Voor OPS donateurs en voor artsen hebben we het volledige studierapport beschikbaar van de universiteit van Freiburg, maar is teveel om hier op de site te zetten.



Active Immunotherapy of Prostate Cancer with a Focus on Dendritic Cells
Recurrent or metastatic prostate cancer is generally considered an incurable disease. Given the transient benefit from hormone deprivation therapy and limited successes of systemic chemotherapy, alternative treatment modalities are needed both in the situation of PSA recurrence and in hormone-refractory disease. Prostate cancer cells express several tumor associated antigens which are currently being evaluated as targets for active and specific immunotherapy approaches. Dendritic cells (DC) are the most powerful antigen-presenting cells (APC), able to prime naïve T cells and to break peripheral tolerance and thus induce tumor immune responses. Close to 1000 prostate cancer patients have been treated with DC-based or other forms of active immunotherapy to date. Vaccination-induced immune responses have been reported in two thirds of DC trials, and favorable changes in the clinical course of the disease in almost half of the patients treated. Most responses, however, were modest and transient. Therefore, mechanisms of treatment failure and possibilities to improve vaccination efficacy are being discussed.
Keywords: Immunotherapy. Prostate cancer. Dendritic cells.
Of the more than 50 immunotherapy trials reported on in peer-reviewed scientific journals, all suggest that active immunotherapy of prostate cancer is safe. Side effects have mainly been restricted to local reactions at the site of injection and mild general reactions such as fever, especially in trials using GM-CSF or IL-2. In addition, the risk of inducing autoimmunity, which may, for example, occur as vitiligo after vaccination for melanoma and may be associated with clinical responses95 may be acceptable given the fact that the prostate represents essentially a dispensable tissue.
The frequency of immune responses and favorable changes in clinical parameters such as reductions in PSA kinetics was variable between trials. In DC-based vaccination, biologic effects were seen in about 45% of the patients. These were underscored by mostly T cell-mediated and some humoral immune responses in about 67% of patients. A comparison of different vaccination strategies is hardly possible due to great differences in patient eligibility criteria and choice of endpoints. In many trials, especially those without DC, reporting of immune monitoring is insufficient, rendering the interpretation of the data difficult and even informal comparisons between trials impossible. Patients' outcome seems to be similar with different vaccination strategies, but the frequencies of responding patients and of long-lasting biologic responses seem to be somewhat higher in virus-or DC-based formulations than in those with adjuvant or genetically engineered tumor cells.
In several studies, correlations between immune responses and clinical effects were observed. In the only randomized, placebo-controlled phase III vaccination trial, a survival benefit of several months for vaccinated patients could be shown60. While the other (i.e., phase I/II) trials cannot provide formal proof for clinical efficacy, their results are encouraging and provide a proof of principle for the immunogenicity of anti-tumor vaccination in prostate cancer patients. To further improve patients' outcome, several strategies involving choice of antigen, optimisation of the vaccine formulation, e.g. by improved DC maturation or development of highly immunogenic vectors, are being explored. Additional approaches to enhance the immunization efficacy are combination with conventional treatment or systemic immune modulation such as removal of Treg. Finally, patients with low tumor burden and better immune competence might profit more from vaccination therapy than heavily pre-treated, advanced-stage cancer patients.
This work was supported by a research grant by the Wilhelm-Sander-Foundation, Germany (to A.-K. T.-K. and H.V.). The authors declare that they have no potential conflicts of interest.

Mei 2002: Bron: Northwest biotherapeutics.

Dendritische cellen als immuuntherapie toegepast bij patiënten met vergevorderde prostaatkanker zorgden in een Phase I/II trial voor veelbelovende resultaten. Bij maar liefst 54,8 % van de deelnemende patiënten stabiliseerde de kanker en dit is volgens de onderzoekers nog nooit vertoond bij patiënten met een dergelijke soort vergevorderde kanker. Aan de hand van deze resultaten is nu dan ook een groot gerandomiseerd en dubbelblind placebo gecontroleerd onderzoek onder 495 patiënten opgezet verdeeld over 22 verschillende ziekenhuizen.


BOTHELL, Wash.--(BUSINESS WIRE)--April 3, 2002--
Dendritic Cell-based Therapy Produces Additional Promising Data From
Trial Targeting Late-Stage Prostate Cancer

Northwest Biotherapeutics, Inc. (Nasdaq:NWBT) announced today that it will
present additional favorable results from the Phase I/II late-stage prostate
cancer clinical evaluation of its dendritic cell-based immunotherapy,
DCVax-Prostate. The data will be presented on Sunday, April 7, 2002, at the 93rd
Annual American Association for Cancer Research (AACR) Meeting in San Francisco,
Dr. Gopi Shankar, Manager of Immune Monitoring and Quality Assurance at
Northwest Biotherapeutics, will present data from 31 late-stage prostate cancer
patients with no other treatment alternatives who received DCVax-Prostate during
a Phase I/II trial conducted at the M.D. Anderson Cancer Center, Houston, and at
UCLA. Northwest Biotherapeutics observed overall stabilization of disease in
54.8% (17 of 31) of the patients in its Phase I/II clinical trial. Twelve of
these patients, each of whom had rising PSA values following hormone therapy,
did not have measurable metastatic disease at the time of treatment initiation.
All twelve were stable, as measured by radiographic criteria, at weeks 23 and
Northwest Biotherapeutics' Chief Medical Officer, Dr. Scott Stromatt, stated,
"We continue to be very encouraged by both the safety profile of DCVax-Prostate
and its clinical impact on the small number of patients treated. No other
treatment methodology that we are aware of has produced such a measurable
positive response in patients with this late stage prostate cancer." Dr.
Stromatt further commented that Northwest Biotherapeutics recently initiated a
495 patient double blind, placebo-controlled trial to further evaluate
DCVax-Prostate as a potential treatment for late-state prostate cancer patients,
which is anticipated to be conducted at 20 to 25 clinical sites in the United
Dr. Stromatt also stated "Cancer continues to be a major health issue in the
United States despite the many medical advances since President Nixon declared
War on Cancer over 30 years ago." The American Cancer Society recently reported
that approximately 1.3 million Americans will be newly diagnosed with cancer in
2002. Prostate cancer is expected to account for almost 15% of these new cancer
diagnoses and to result in just over 30,000 male deaths this year.


Development stage: DCVax®-Prostate is entering a Phase III clinical trial that was cleared to proceed by the Food and Drug Administration in January of 2005. Data from a Phase I/II clinical trial support the overall safety of DCVax®-Prostate, and suggest that DCVax®-Prostate may induce an immune response . Clinical data obtained in this trial also suggest delayed times to progression of disease, especially in patients with no metastatic disease at entry.

Trial design: The Phase III clinical trial is a randomized, multi-center, double blinded clinical trial that will enroll 612 patients in the United States.

Indication: Patients with hormone independent, non-metastatic prostate cancer will be eligible for participation in this clinical trial. Other eligibility criteria include requirements around absolute PSA levels as well as PSA doubling time.

Endpoints: The primary endpoint for the Phase III clinical trial is survival free of disease progression. The first secondary endpoint is survival free of the development of symptoms arising from progression of disease. Other endpoints include the induction of immune responses, and overall survival.

Product: DCVax®-Prostate is manufactured using a patient’s own dendritic cells, loaded with a recombinant form of Prostate Specific Membrane Antigen (rPSMA). The dendritic cells are generated from monocytes obtained through a single leukapheresis.

Immunization schedule: Immunization starts when eligible patients have met all entry criteria, including the specified absolute PSA level and PSA doubling time. Immunizations will be given at weeks 0, 2, 4, 8, and at months 3, 6, 9, 12, 18, 24 and 30.


Previous Phase I/II Clinical Trials

The Phase I/II study evaluated 32 patients with hormone independent prostate cancer, both non-metastatic and metastatic. Twelve patients entered the study with no radiological evidence of metastatic disease, and 20 had between one and three bone and/or lymph node metastases.

The natural history of prostate cancer indicates that patients with rising PSA values while on hormone treatment progress to metastatic disease on average in about 28-36 weeks, dependent upon several prognostic factors such a PSA velocity, time on anti-androgen therapy and nadir PSA while on anti-androgen therapy. In the non-metastatic group of patients (n=12), none had progressed at 28 weeks and only half had progressed at 59 weeks. Based on these Phase I/II data, the delay of progression to metastatic disease during long-term follow-up of this subset of patients appears correlated with stabilization of PSA levels. This is the patient population that the company will focus on in the Phase III clinical trial.
We also measured a highly specific PSMA antibody response following immunization with DCVax®-Prostate, and a highly specific and strong T cell response to PSMA in about 80% of the patients treated with DCVax®-Prostate. Northwest Biotherapeutics’ expectation based on these data is that administration of DCVax®-Prostate will enhance progression free survival relative to placebo, delay the development of symptomatic disease and increase overall survival.

Bron: Universitet van Freiburg

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