Intratumoral and Systemic Hiltonol® (Poly-ICLC) in Prostate Cancer Patients on Active Surveillance

Inclusion Criteria: * Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Age \> 18 years at the time of consent. * ECOG Performance Status of 0-1 within 14 days prior to being registered for protocol therapy (Study Procedure Manual). * Histologically confirmed adenocarcinoma of the prostate (with previous diagnostic tissue available for tumor marker analysis). * • ISUP Grade 1(Gleason 3+3) and Grade 2 (Gleason 3+4) and Grade 1 (Gleason 3+3, with PSA≥10, or stage ≥ T2b) * Estimated life expectancy is ≥ 10 years * Candidate for primary curative therapy (Radical prostatectomy or radiation) if cancer progresses. * Tolerated previous transrectal ultrasound guided biopsy procedure under local anesthetic * Uncomplicated previous TRUS biopsy procedure (i.e., no prior hospitalization due to sepsis, prostatic abscess or severe hemorrhage following TRUS prostate biopsy) * Willing to undergo the intratumoral (IT) injection of the Poly-ICLC into the prostatic tumor as per the protocol * No prior hormonal therapy with exception of with the exception of oral 5-alpha-reductase inhibitors (finasteride, dutasteride, etc.). Subjects should be off the medication ≥ 6 months from screening * No prior radiation therapy (external beam or brachytherapy) to the pelvis or prostate. * No clinically significant infections as judged by the treating investigator. * No characteristics suggesting a potential higher risk of infection with intraprostatic injections: * Recurrent urinary tract infections or history of prostatitis within 3 months prior to enrollment into the study. * Urine analysis positive for nitrites and leucocyte esterase. Such subjects could be considered for the study after treatment and resolution of the infection. * Active proctitis * History of prostatic abscess * Taking immunosuppressive medication including systemic corticosteroids * Active hematologic malignancy * No uncontrolled angina, congestive heart failure or MI within 6 months. * Subjects with history of HIV (if CD4+ T cell counts are ≥350 cells/μL on established ART therapy), Hepatitis B (with viral load below limits of quantification) or Hepatitis C (who have completed a curative therapy and have a viral load below the limit of quantification) are eligible for this study. * No treatment with any investigational agent for any medical condition within 28 days prior to being registered for protocol therapy. * Patients with the potential for impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Contraception must be continued for at least 2 months following the last dose of poly-ICLC. While animal reproductive studies have been negative, the simulated viral infection and anti-proliferative activity of this experimental drug may theoretically affect the developing fetus or nursing infant. * Adequate end organ function as determined by the following laboratory values: * White blood cell count (WBC) ≥ 2.5 k/mm\^3 * Absolute neutrophil count (ANC) ≥ 1.5 k/mm\^3 * Hemoglobin (Hgb) ≥ 8.0 g/dL * Platelets ≥ 100 k/mm\^3 * Calculated creatinine clearance of \> 60 cc/min using the Cockcroft-Gault formula: * Males: \[(140 - Age in years) × Actual Body Weight in kg\]/\[72 × Serum Creatinine (mg/dL)\] * Bilirubin ≤ 2.0 x ULN * Aspartate aminotransferase (AST) ≤ 2.5 x ULN * Alanine aminotransferase (ALT) ≤ 2.5 x ULN Exclusion Criteria: * Received local or systemic curative therapy for prostate cancer * Subjects with neuroendocrine tumors * ISUP Gleason Grade Group (\>3), or Gleason 3+3 plus PSA ≤ 10 or Stage ≤T2a * Evidence of locally advanced disease * Subject has evidence of any other malignancy * Allergy to any antibiotics, as IT administration requires prophylactic antibiotics.