DCreg in Living Donor Liver Transplantation

Phase I/II, single center, prospective, open-label, non-controlled, non-randomized,
interventional, cohort study in which low risk living donor liver transplant (LDLT)
recipients will receive a single infusion of donor-derived DCreg with concurrent mycophenolic
acid (MPA) therapy (1/2 dose) 1 week prior to transplantation. All patients will be
maintained on MPA and Tacrolimus (Tac) for the 1st 6 months after transplantation. At that
time point, recipients meeting specific criteria (no rejection and permissive liver function
tests (LFTs)) will be slowly weaned off MPA per standard of care over a period of 6 months.
Participants will then be evaluated for TAC weaning at 1 yr after transplantation. Those who
meet the criteria of no rejection and permissive LFTs will undergo a protocol liver biopsy
and proceed to Tac weaning over 6 months if liver biopsy is permissive. Successfully weaned
participants who remain rejection-free will undergo 3 years of follow-up after the last dose
of immunosuppression. They will undergo a liver biopsy at 1 yr and 3 yrs after
immunosuppression withdrawal. Participants who are removed from the study protocol at any
time will return to standard of care, but will be continue to be followed by the study team
and will undergo a liver biopsy at the end of the study (4.5 yrs after transplantation).

Inclusion Criteria:

Donors

1. Able to understand and provide informed consent;

2. Male or female between the ages of 18-55;

3. Meet all standard institutional and UNOS criteria for liver donation;

4. For females of childbearing potential, a negative urine or serum pregnancy test;

5. Negative for HIV (5th generation Test and NAT), HTLV-1, HTLV-2;(*)

6. Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and NAT)(*)

Recipients

1. Low risk recipient approved for LDLT, irrespective of gender, race, or ethnic
background. Low risk is defined by absence of exclusion criteria (below).

2. Between ages 18 and 65 years

3. Undergoing de novo (first) liver transplant

4. Female subjects of childbearing potential must have a negative pregnancy test upon
study entry.

5. Agreement to use contraception; according to the FDA Office of Women's Health
(http://www.fda.gov/birthcontrol), there are a number of birth control methods that
are more than 80% effective. Female participants of child-bearing potential must
consult with their physician and determine the most suitable method(s) from this list
to be used from the time that study treatment begins until 1 year after completion of
immunosuppression withdrawal.

(*)does not preclude donors from undergoing leukapheresis but cells may not be infused into
recipient.