Inclusion Criteria:
* Written informed consent obtained prior to the initiation of study procedures.
* Patients who meet the US FDA-approved indication for Sipuleucel-T: for asymptomatic or minimally symptomatic mCRPC at the discretion of the treating investigator.
* Histologically confirmed adenocarcinoma of the prostate.
* Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone scan and/or computed tomography (CT) scan or Magnetic Resonance Image (MRI).
* Progressive castration-resistant prostate cancer (CRCP): Participants must have current or historical evidence of disease progression concomitant with surgical or medical castration and during immediate past systemic therapy, as demonstrated by (a) PSA progression, or (b) progression of measurable disease, or (c) progression of non-measurable disease as defined below:
1. By PSA: two consecutively rising PSA values, at least 7 days apart, each ≥ 1.0 ng/mL and ≥ 50% above the minimum PSA observed during castration therapy or above the pre-treatment value if there was no response.
2. By measurable disease: Progressive disease by RECIST v1.1 criteria
3. By non-measurable disease
i. Soft tissue disease: The appearance of 1 or more new lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response.
ii. Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression.
* Castration status confirmed by serum testosterone level \<50ng/dL
* ECOG Performance Status of 0 or 1.
* Adequate liver function:
1. Bilirubin \<2.0 x institutional upper limit of normal (UNL)
2. AST (SGOT) \<2.5 x UNL
3. ALT (SGPT) \<2.5 x UNL
* Acceptable renal function
a) Serum creatinine \<2.0 x UNL
* Acceptable hematologic function:
1. Absolute neutrophil count (ANC) \> 1.0 x10\^9 cells /L)
2. Platelet counts \> 100 x 10\^9 / L)
3. Hemoglobin \>9 g/dL
Exclusion Criteria:
* PSA \>20ng/dL within the 4 weeks prior to signing ICF
* Previously treated with three or more FDA-approved androgen/AR signaling inhibitors (ASI) (e.g., abiraterone, enzalutamide, apalutamide, darolutamide). No minimum number of ASI is required.
* Prior chemotherapy for mCRPC. However, prior chemotherapy administered for mCSPC is allowed unless the disease progression to CRPC occurred within 12 months from the last dose of chemotherapy.
* Prior treatment with Sipuleucel-T or supraphysiologic dose of testosterone treatment for prostate cancer.
* Prior systemic treatment with ASI, PARP inhibitor or Radium-223 or other systemic anti-cancer therapy for prostate cancer within 4 weeks prior to start of treatment.
* Prior prednisone \>10mg (or its equivalent) within 2 weeks prior to registration.
* Prior immunotherapy or Lu177 PSMA radioligand therapy within 6 weeks prior to registration.
* Prior palliative radiotherapy within 2 weeks prior to registration.
* Radiographic evidence of hepatic metastases
* Use of narcotics including tramadol or stronger for cancer-related pain within 4 weeks prior to signing ICF. Use of NSAIDs or acetaminophen is allowed.
* Active autoimmune disease requiring systemic corticosteroids of prednisone greater than 10mg a day or the equivalent dose of other corticosteroids.
* Known active HIV, Hepatitis B or Hepatitis C or Human T cell Lymphotropic virus (HTLV)-1 infection. Testing is not required. Note: Participants with resolved, historic HIV, Hepatitis B or Hepatitis C or Human T cell Lymphotropic virus (HTLV)-1 will be assessed by the PI and deemed eligible if their viral infections are in remission: without detectable viruses and secondary immunodeficiency, and without requiring any treatments that affects immune function. Eligibility will be determined after a discussion with the PI and adequate standard clinical tests are acquired to prove that they are in remission.
* Active infection requiring parenteral antibiotic therapy or causing fever (temperature \>100.5 in Fahrenheit scale) within 1 week prior to registration.
* Life expectancy of less than 6 months prior to signing ICF.
* Any medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives.
