Natural Dendritic Cells for Immunotherapy of Chemo-naive Metastatic Castration-resistant Prostate Cancer Patients

Inclusion Criteria:

* Men ≥ 18 years of age and older with confirmed (histologically or cytologically) adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
* Human leukocyte antigen (HLA)-A2.1 positive
* Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)
* Metastatic castrate-resistant disease defined as one or more of the following criteria that occurred while the patient was on androgen deprivation therapy:

  * Prostate-specific antigen (PSA)-progression defined by Prostate Cancer Working Group 2 (PCWG2) criteria by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination
  * Progression of nodal metastases defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria or progression on successive magnetic resonance imaging lymphangiographies (MRLs)
  * Bone disease progression defined by two or more new lesions on bone scan as described in PCWG2 criteria
* Maintenance of castrate circumstances:

  * Ongoing primary androgen deprivation therapy (Gonadotropin-Releasing hormone agonist or antagonist) or bilateral orchiectomy
  * Serum testosterone level ≤ 1.73 nmol/L (50 ng/dL) at screening visit
* PSA value ≥ 2 ng/ml
* Absence of visceral metastases, malignant ascites or pleural effusion
* Clinical absence of brain metastases
* Inclusion within three months after the moment of manifestation of progressive disease as defined above
* Chemotherapy naive
* Life expectancy ≥ 6 months
* World Health Organization/Eastern Cooperative Oncology Group performance status 0-1 (Karnofsky index 100-70)
* White blood cells \>2.0x109/l, neutrophils \>1.5x109/L, lymphocytes \>0.8x109/L, platelets \>100x109/L, hemoglobin \>5,6 mmol/L (9.0 g/dL), serum creatinine \<150 µmol/L, aspartate aminotransferase/alanine aminotransferase \<3 x upper limit of normal (ULN), serum bilirubin \<1.5 x ULN (exception: Gilbert's syndrome is permitted)
* Expected adequacy of follow-up
* Written informed consent

Acceptable concomitant therapy:

* The use of oral or intravenous bisphosphonates
* Radiotherapy for pain relief in patients with bone metastases may be used as a treatment modality, but the need for a radiotherapeutic intervention during the study will be documented as an skeletal-related event (SRE)
* Inhaled corticosteroids and topical creams for small body areas are permitted

Exclusion Criteria:

* Hypercalcemia
* History of any second malignancy in the previous five years, with the exception of adequately treated basal cell carcinoma
* Known allergy to shell fish
* Heart failure (New York Heart Association class III/IV)
* Serious active infections
* Active hepatitis B, C or HIV infection
* Active syphilis infection
* Autoimmune diseases (exception: vitiligo is permitted)
* Organ allografts
* An uncontrolled co-morbidity, e.g. psychiatric or social conditions interfering which participation
* Previous treatment with sipuleucel-T,PROSTVAC, GVAX, chemotherapy, ipilimumab or denosumab (previous treatment with abiraterone acetate, ketoconazole or enzalutamide is permitted)
* Treatment with flutamide, bicalutamide, or nilutamide within four weeks of study enrollment
* Prior radiotherapy within four weeks prior to planned vaccination or presence of treatment-related toxicity
* Continued use of non-steroidal anti-inflammatory drugs
* Concurrent use of systemic corticosteroids \> 10 mg daily prednisone equivalent
* Requirement of opiate use for cancer-related pain (at screening)
* Any serious clinical condition that may interfere with the safe administration of DC vaccinations