Inclusion Criteria:
To be eligible for this study, patients must meet all of the following criteria:
* Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs by CT or NM bone scan. N1 by PSMA allowed with up to 3 LNs each ≤1 cm. If there is no frank bone disease, but PSMA scan and CT scan are in discordance, then investigators will discuss.
* Initial prostate biopsy, obtained within 3 months of enrollment, is available for central pathologic review, and is confirmed to show at least 3 positive cores (at least 1 core with at least 50% disease involvement with ≥4+3=7 disease) and a Gleason sum of ≥8 (or 4+3=7 with at least 1 additional high-risk feature such as PSA\>20 or cT3)
* Radical prostatectomy has been scheduled
* Age ≥18 years
* ECOG performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)
* Adequate bone marrow, hepatic, and renal function:
* WBC \>3,000 cells/mm3
* ANC \>1,500 cells/mm3
* Hemoglobin \>9.0 g/dL
* Platelet count \>100,000 cells/mm3
* Serum creatinine \<1.5 × upper limit of normal (ULN)
* Serum bilirubin \<1.5 × ULN
* ALT \<3 × ULN
* AST \<3 × ULN
* Alkaline phosphatase \<3 × ULN
* The etiology of abnormal bilirubin and transaminase levels should be evaluated prior to study entry.
* Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
* Willingness to use barrier contraception from the time of first dose of Enoblituzumab (MGA271) until the time of prostatectomy.
Exclusion Criteria:
To be eligible for this study, patients should not meet any of the following criteria:
* Presence of known lymph node involvement on CT (N1 by PSMA allowed with up to 3 LNs each ≤1 cm) or distant metastases by CT and NM bone scan
* Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors
* Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer
* Prior immunotherapy/vaccine therapy for prostate cancer
* Prior use of experimental agents for prostate cancer
* Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors
* Current use of systemic corticosteroids or use of systemic corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or COPD are permitted as are other non-systemic steroids such as topical corticosteroids)
* History or presence of autoimmune disease requiring systemic immunosuppression (including but not limited to: inflammatory bowel disease, systemic lupus erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis, hemolytic anemia, Sjögren syndrome, and sarcoidosis)
* History of malignancy within the last 3 years, with the exception of non-melanoma skin cancers and superficial bladder cancer
* Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate
* Known prior or current history of HIV and/or hepatitis B/C, with the exception of patients who have been successfully treated for hepatitis B/C (i.e. documented confirmation of cure at least 6 months after initial treatment).
