Donor Alloantigen Reactive Tregs (darTregs) for Calcineurin Inhibitor (CNI) Reduction

Study Enrollment Inclusion Criteria:

• Subjects who meet all of the following criteria are eligible for enrollment:
• Able to understand and provide informed consent
• Have received a primary, solitary, living donor liver transplant more 24 months and less than 84 months ago
• Have a living donor who is willing to consent to a one time blood draw of 100 mLs to enable the manufacture of Donor Alloantigen Reactive Regulatory T cells (darTregs)
• Eighteen to 70 years of age at the time of study entry/consent
• Liver function test (LFT) results: have Alanine Aminotransferase (ALT)consistently <60 U/L and either alkaline phosphatase consistently <150 U/L or Gamma-glutamyl transferase (GGT) consistently <60 U/L
• Currently receiving a Calcineurin Inhibitor (CNI) with 12 hour trough levels consistently <6.0 ng/mL for tacrolimus; <150 ng/mL for cyclosporine
• Currently receiving CNI monotherapy or CNI and one of the following:
• Prednisone: maximum dose of 5mg daily
• Mycophenolate mofetil (MMF): maximum dose of 500 mg administered twice daily for Cellcept or 360mg twice daily for Myfortic.
• Female and male participants with reproductive potential must agree to use effective methods of birth control for the duration of the study.
• If history of Hepatocellular carcinoma (HCC), liver transplantation (LT) recipients who have:
• α-fetoprotein (AFP) less than 100 μg/L at the time of transplant AND
• Explanted liver:
• with tumor burden within the Milan criteria and
• without macro- or micro-vascular invasion and
• without any lesions with poorly differentiated HCC and
• without cholangiocarcinoma morphology
• Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score less than or equal to 3
• If history of HCC, at the time of enrollment, subjects must also:
• Be 36 months or more post-transplant AND
• Without evidence of recurrent HCC defined as:
• AFP within normal limits for performing laboratory;
• Confirmatory chest CT and
• Confirmatory CT or MRI of the abdomen and pelvis.
• If history of hepatitis C virus (HCV) , recipients must be:
• Cured of HCV as defined by achieving Sustained virologic response (SVR) and be greater than or equal to six months after the end of treatment
• HCV RNA negative at time of study enrollment

Study Enrollment Exclusion Criteria:

• Participants who meet any of these criteria are not eligible for study enrollment:
• Transplant for liver disease secondary to autoimmune disease (e.g. autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cirrhosis)
• Matched at both human leukocyte antigen (HLA)-DR loci to the donor
• Organ, tissue or cell transplant prior to or after the primary solitary living donor liver transplant
• For subjects with hepatitis B, detectible hepatitis B virus (HBV) DNA
• History of malignancy within 5 years of enrollment. History of adequately treated in-situ cervical carcinoma and/or skin cancer (basal or squamous cell) will be permitted.
• Serologic evidence of human immunodeficiency 1 or 2 infection
• Epstein Barr Virus (EBV) seronegativity (EBV naïve) if living donor is EBV seropositive
• Cytomegalovirus (CMV) seronegativity (CMV naïve) if living donor is CMV seropositive
• Calculated Glomerular filtration rate (GFR) less than 50 mL/min/1.73m^2 at the time of enrollment
• An episode of Acute Rejection (AR) within one year of enrollment
• Systemic illness requiring or likely to require recurrent or chronic immunosuppression (IS) drug use
• Any chronic condition for which anti-coagulation cannot be safely interrupted for liver biopsy
• Positive pregnancy test
• Participation in any other studies that involved investigational drugs or regimens in the preceding year
• Any other condition, in the investigator's judgment, that increases the risk of darTregs infusion or prevents safe trial participation
• Unwilling or unable to adhere to study requirements and procedures
• Screening liver biopsy with any of