Liver Transplantation With Tregs at UCSF

The researchers in this study plan to enroll 9 participants. Eligible participants will
receive a single dose of Treg product (arTreg). The target dose is 100 to 500 x 10^6 total
cells. However, if a minimum arTreg dose of 30 to < 100 x 10^6 cells is manufactured, the
product will be infused. Participants who receive at least the minimum arTreg dose
referenced, as a result of low cell yield, will be included in intent-to-treat (ITT)
analysis.

Participants who successfully withdraw from all immunosuppression will undergo a research
biopsy at 52 weeks following drug discontinuation to determine whether they meet the primary
efficacy outcome of operational tolerance. Participants determined to be operationally
tolerant will be followed until 104 weeks following drug discontinuation and have a research
biopsy at that time to confirm that they remain operationally tolerant. Participants who fail
drug withdrawal after 52 weeks but before 104 weeks will be followed until week 104 or 12
weeks after resuming immunosuppression, whichever is longer. The research biopsy at week 104
will be optional for these participants.

Participants who do not successfully withdraw from all immunosuppression will complete 104
weeks of High Intensity Safety Follow-up after failing immunosuppression withdrawal.

*** IMPORTANT NOTICE: *** The National Institute of Allergy and Infectious Diseases and the
Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy
for recipients of cell, organ, or tissue transplants outside of physician-directed,
controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can
result in serious health consequences and should only be performed in certain rare
circumstances, upon the recommendation and with the guidance of your health care provider.

Inclusion Criteria:

Eligibility:

Recipient:

- Individuals must meet all of the following criteria to be eligible for this study:

1. Able to understand and provide informed consent

2. End-stage liver disease and listed for a living or deceased-donor primary
solitary liver transplant

3. Agreement to use contraception

4. Negative test for hepatitis C infection by hepatitis C virus (HCV) PCR RNA

5. For candidates with a history of HCV, completed treatment for HCV

6. Positive Epstein-Barr virus (EBV) antibody test and

7. Immunizations are up-to-date based on the Advisory Committee on Immunization
Practices (ACIP) recommendations, unless the investigator determines that
administering a recommended immunization is not in the participant's best
interest.

Living Donor:

- Living donors must meet all of the following criteria to be eligible for this study:

1. Able to understand and provide informed consent

2. Meets site-specific clinical donor eligibility requirements

3. Meets donor eligibility manufacturing requirements within 7 days prior to blood
collection for manufacturing and

4. Willingness to donate appropriate biologic samples.

Deceased Donor:

Deceased donors must meet the following criteria for their recipients to be eligible for
this study:

1. Meets site-specific clinical donor eligibility requirements and

2. Meets donor eligibility manufacturing requirements.

Note:

- There are several stages to this study.

- Eligibility is evaluated at many time points during the study to assess whether a
participant is safe to proceed to the next study stage.

Exclusion Criteria:

Recipient:

-Individuals who meet any of the following criteria will not be eligible for this study:

1. History of previous organ, tissue or cell transplant requiring or potentially
requiring immunosuppression

2. For cytomegalovirus (CMV) antibody negative recipients, a (CMV) antibody positive
donor

3. Known contraindication to cyclophosphamide or Mesna administration

4. Serologic evidence of human immunodeficiency virus (HIV)-1/2 infection

5. The need for chronic anti-coagulation that cannot be safely discontinued for a minimum
of 1 week to safely perform a liver biopsy

6. End stage liver disease secondary to autoimmune etiology (autoimmune hepatitis,
primary biliary cirrhosis, or primary sclerosing cholangitis) or other
contraindications to drug withdrawal

7. Psychological, familial, sociological or geographical factors potentially hampering
compliance with the study protocol and follow-up visit schedule

8. Any form of substance abuse, psychiatric disorder, or other condition that, in the
opinion of the investigator, may interfere with study compliance

9. Use of investigational drugs within 8 weeks of study enrollment

--Note: Participation in a concurrent ex vivo liver perfusion study is not
exclusionary

10. History of ischemic heart disease requiring revascularization, history of or current
treatment for dysrhythmia, or evidence of congestive heart failure, unless cleared by
a cardiologist

11. Past or current medical problems, treatments or findings that are not listed above,
which, in the opinion of the investigator, may:

-- pose additional risks from participation in the study,

-- interfere with the candidate's ability to comply with study requirements, or

- impact the quality or interpretation of the data obtained from the study.

12. History of malignancy with a risk of recurrence judged by the investigator to be >1%,
except for:

-- hepatocellular carcinoma,

- adequately treated in-situ cervical carcinoma, or

- adequately treated basal or squamous cell carcinoma of the skin.

13. Chronic use of systemic glucocorticoids or other immunosuppressives, or biologic
immunomodulators.

Living Donor:

Living donors who meet the following criteria will not be eligible for this study:

1. Any condition that, in the opinion of the investigator, may pose additional risks from
participation in the study, may:

- interfere with the participant's ability to comply with study requirements or

- impact the quality or interpretation of the data obtained from the study.

Deceased Donor:

Recipients of livers from deceased donors who meet the following criteria are ineligible
for this study:

1. Any condition that, in the opinion of the investigator, may pose additional risks or may
impact the quality or interpretation of the data obtained from the study.