2.1.2.13 Patients with prior chemotherapy for nonmetastatic prostate cancer within a year are excluded. 2.1.2.14 Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs. (Immune checkpoint inhibitors that are antibody-based will only require 28 days before enrollment) 2.1.2.15 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension (SBP>170/ DBP>105) or psychiatric illness/social situations within 12 months that would limit compliance with study requirements. 2.1.2.16 Use of herbal products that may decrease PSA levels (e.g. saw palmetto) 2.1.2.17 Any gastrointestinal disease that could hinder the absorption of enzalutamide. 2.1.2.18 Patients who have had chemotherapy for metastatic castration-resistant prostate cancer. (Patients who have had docetaxel for metastatic castration sensitive disease per CHAARTED Data[34] may enroll as long as they did not have progressive disease 22 Short Title: Enzalutamide Vaccine in mCRPC Version Date: 03/29/2022 while on docetaxel and are 6 months removed from treatment, with all treatment related toxicities resolving to at least grade 1.) 2.1.2.19 Patients who have received radiation therapy, radionuclide therapy or undergone surgery within certain duration (4 weeks) of enrollment 2.1.3 Recruitment Strategies This study will be listed on available websites (www.clinicaltrials.gov) and participants will be recruited from the current patient population at NIH and participating sites. 2.2 SCREENING EVALUATION Note: Screening evaluation testing/procedures are conducted under the separate screening protocol, 01-C-0129 (Eligibility Screening and Tissue Procurement for the NIH Intramural Research Program Clinical Protocols).