Retro-active Immunological Tolerance in Patients With Well-functioning Pre-existing HLA-identical Kidney Transplants

For people ages 18 years and up

Recipient Inclusion Criteria:

1. Donor is identical twin.
2. ABO incompatibility with donor
3. Positive HLA Donor-Specific Antibody (DSA)
4. Multi-organ transplantation
5. History of rejection with current HLA matched kidney transplant
6. Known allergy to rabbit proteins
7. History of malignancy within the past 5 years with the exception of non-melanomatous skin cancer and low risk, early-stage malignancy with ≥90% 5-year survival not receiving chemotherapy or immunotherapy.
8. History of post-transplant major complications, including de novo malignancy, active/chronic infection or rejection, with the exception of low risk, early-stage malignancy with ≥90% 5-year survival not receiving chemotherapy or immunotherapy, and non-melanomatous skin cancer.
9. History of another primary malignancy except for:
   1. Malignancy treated with curative intent and with no known active disease > 2 years before the first dose of study treatment and of low potential risk for recurrence
   2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
   3. Very low risk and low risk cancer adequately treated or on active surveillance
   4. Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ, and DCIS)
10. Worsening renal functioning over preceding 3-month interval, defined as eGFR exceeding 30% of baseline value.
11. Pregnant (confirmed by urine or serum pregnancy test) or lactating.
12. Leukopenia (with a white blood cell count < 3,000/µL) or thrombocytopenia (with a platelet count < 70,000/µL).
13. Participants should be EBV, CMV and BK PCR negative at time of HPSC infusion. If participants have had a history of + EBV/CMV/BK PCR, it should be resolved by 3 months. Participants will be rescreened at 3 months. If they remain seropositive, they will be excluded from the study.
14. Active bacterial, fungal, mycobacterial, or viral infection (including active hepatitis B and/or C).
15. Seropositivity for HIV 1 or 2 by 4th generation serum antibody/antigen testing, or HTLV I or II by serum antibody testing.
16. Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis).
17. Advanced hepatic fibrosis or cirrhosis secondary to hepatitis B and/or C diagnosis.
18. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia; active extra-renal autoimmune disease requiring immunosuppression.
19. Active extra-renal autoimmune disease requiring immunosuppression.
20. Neuropsychiatric illness that precludes the ability to give informed consent and/or places the participant as high risk for non-compliance with the safety monitoring requirements of the study.
21. May not have received other immunomodulatory agents, including but not limited to tumor necrosis factor inhibitors within six months of the study treatment. Use of corticosteroids prescribed for a time-limited indication (</= 4 weeks) and stopped at least 4 weeks before the kidney transplant is acceptable.
22. May not have received immunotherapy drugs such as immune checkpoint inhibitors (e.g. pembrolizumab, nivolumab, and ipilimumab), tumor necrosis factor inhibitors, rituximab, and interleukin-2 within six months of the study treatment.
23. Current or active abuse of alcohol and/or drugs within last 6 months.
24. Body Mass Index (BMI) ≥ 40.

Donor Inclusion Criteria:

1. HLA-identical sibling on high-resolution HLA typing who is ≥18 years of age.
2. Must meet institutional criteria for HSPC transplant donation.
3. Medically fit to tolerate peripheral blood apheresis, including weighing ≥110 pounds, hemoglobin ≥11, white blood cell count ≥ 3,000/µL, and platelets ≥ 120,000/µL.
4. Serum creatinine as expected post kidney donation and coagulation parameter studies; or, if abnormal, the changes are not considered clinically significant.

Donor Exclusion Criteria

1. Recipient is identical twin.
2. ABO incompatibility with recipient.
3. Medically unfit to tolerate peripheral blood apheresis (e.g.: small body size, poor vascular access, not a suitable candidate for placement of a central catheter).
4. Pregnant (confirmed by urine or serum pregnancy test) or lactating.
5. Seropositivity for HIV 1 or 2 by 4th generation serum antibody/antigen testing, HTLV I or II by serum antibody testing
6. Active West Nile Virus infection
7. Active bacterial, fungal, mycobacterial or viral infection (including active hepatitis B and/or C).
8. Psychiatric, addictive, neurological, or other disorder that compromises ability to give true informed consent for participation in this study.
9. History of active malignancy within the past 5 years with the exception:
   1. Adequately managed malignancy within the past two years with low risk of recurrence may be acceptable as per clinician discretion
   2. Adequately managed non-melanoma skin cancer
   3. Adequately managed carcinoma in situ e.g., cervical cancer in situ, and DCIS
10. No current or recent use of oral anti-coagulants. (For the purpose of this study, recent is defined as less than 60 days prior to apheresis.). Note: Use of aspirin and non-steroidal anti-inflammatory drugs, for pain and inflammation management purposes, are permitted to enroll in the study, but these drugs must be stopped 14 days prior to apheresis, however subjects who are taking aspirin for its anti-platelet/anti-thrombotic effect, are excluded.