Inclusion Criteria:
* 1\. Adult men or women aged 18 to 65 years with end-stage kidney disease who are waiting for kidney transplant and require desensitization to enable safe kidney transplant.
2\. Cohort 1:
* A living donor who meets criteria for kidney donation based on national and local center-specific guidelines has been identified
* Highly sensitized participants with a requirement of positive flow cytometry crossmatch, resulting from at least one DSA detected using Luminex SAB during or before Screening
* A positive virtual crossmatch, using Luminex SAB (MFI ≥ 2000), obtained within 30 days of Screening and during Screening
Cohort 2:
* PRA greater than or equal to 80% which is consistent with highly sensitized based on national criteria
* At least one anti-HLA antibody that is unacceptable for kidney transplantation 3. High-resolution HLA typing for both the recipient and the donor within 2 years of Screening.
4\. The participant is currently eligible for transplantation according to local standards if a graft becomes available upon completion of treatment with the study intervention.
5\. Hemoglobin ≥ 8 g/dL. 6. ANC ≥ 800/μL. 7. Absolute lymphocyte count ≥ 2000/μL or CD3 T cell count ≥ 500/μL. 8. Platelet count ≥ 75000/μL. 9. Vaccinations must be up to date in accordance with the national and local center guidance for transplant participants.
10\. Positive for EBV capsid IgG. 11. Testing for latent TB infection must be negative within 3 months prior to Screening. Testing should be conducted using either a purified protein derivative or an IFN-γ release assay (ie, QuantiFERON-TB or T-SPOT.TB). Participants with a positive test for latent TB infection must complete appropriate therapy for LTBI.
A participant is considered eligible if he/she has a negative test for LTBI within 3 months prior to Screening, or if he/she has completed appropriate LTBI therapy prior to transplantation. Treatment for latent TB infection should follow national guidelines.
12\. Participants must be willing to be hospitalized for at least 2 weeks from the time of AZD0120 infusion and must reside within 2 hours of the hospital for an additional 2 weeks following hospital discharge.
13\. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
14\. Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
15\. Nonsterilized male participants who are sexually active with female partner of childbearing potential (See Appendix D for details):
(a)Must agree to use one highly effective method of birth control for at least 3 years post AZD0120 infusion.
(b)For participants who receive LDC but not AZD0120, the contraception time lasts from enrollment until 6 months after the last dose of LDC.
(c)Must refrain from fathering a child or donating sperm within 3 years post AZD0120 infusion.
(d)Female partner of a male participant must use one highly effective method of birth control for at least 3 years post AZD0120 infusion.
16\. Female participants (See Appendix D for details):
1. FOCBP who are sexually active with a non-sterilized male partner must agree to use one highly effective method of birth control for at least 3 years post AZD0120 infusion. For FOCBP participants who receive LDC but not AZD0120, the contraception time lasts from enrollment until 12 months after the last dose of LDC. Cessation of contraception after this point should be discussed with a responsible physician.
2. All FOCBP must have a negative serum pregnancy test result 3 days prior to enrollment at Screening.
3. Must refrain from donating ova within 3 years post AZD0120 infusion.
Exclusion Criteria:
* 1\. Previous solid organ (except kidney) or bone marrow transplant. 2. Complement 3 glomerulopathy, immune-complex mediated membranoproliferative glomerulonephritis, or focal and segmental glomerulosclerosis as the cause of ESKD in the native kidney.
3\. Severe peripheral arterial disease is defined by the presence of resting pain and/or non healing skin ulcers.
4\. History of recurrent UTI; 2 in 6 months or 3 in one year. 5. Active invasive bacterial, viral or fungal infection. Additionally, any infection requiring hospitalization and IV antibiotics within 4 weeks of Screening or PO antibiotics within 2 weeks.
6\. History of HIV regardless of treatment. 7. Evidence of active hepatitis B infection based on positive HBsAg or positive core antibody (anti HBc): participants with positive anti-HBc but negative HBsAg may be enrolled if the HBV DNA test result is negative during the Screening Period.
8\. Evidence of active hepatitis C infection - Positive HCV antibody: Participants with positive HCV antibody and negative HCV RNA test during the Screening Period and absence of cirrhosis may be enrolled.
9\. Detectable viral load for CMV, EBV, BKV or SARS-CoV-2, as determined by PCR. 10. CMV serology incompatible with donor (eg, a recipient with a CMV negative serology should not receive an organ from a CMV positive donor).
11\. History of cirrhosis or severe liver disease, including abnormal liver profile (AST, ALT, or total bilirubin \> 3 × ULN at Screening, except for participants whose hyperbilirubinemia is attributed to Gilbert's syndrome).
12\. History of sickle cell disease or systemic amyloidosis. 13. Any chronic illness requiring uninterrupted anticoagulation or antiplatelet therapy, except for clinical stable and asymptomatic conditions (eg, chronic atrial fibrillation).
14\. Active and severe disease requiring prolonged immunosuppressive therapy, except for low dose glucocorticoids (prednisone or prednisone equivalent \< 10 mg/day).
15\. Receiving ongoing immunosuppressive treatment, including corticosteroids (excepting \< 10 mg/d of prednisone or prednisone equivalent), IV immunoglobulin, CYC, mycophenolic acid, or azathioprine, from 90 days prior to Screening.
16\. CNI use within 14 days prior to Screening. 17. Any B cell depleting or monoclonal antibody therapy within 6 months prior to enrollment.
18\. Cardiac clearance for transplant \> 6 months old and/or any of the following conditions: NYHA Class III or IV heart failure, unstable angina, LVEF \< 40%, a history of recent (within 6 months of Screening) myocardial infarction or presence of implantable cardioverter/defibrillators and/or biventricular pacing.
19\. Moderate-severe pulmonary function abnormality, defined as resting oxygen saturation \< 92% on room air or FEV1, total lung capacity, or DLCO (after correction for hemoglobin) \< 50% of predicted values within 6 months of Screening.
20\. Known life-threatening allergies, hypersensitivity, or intolerance to AZD0120 or its excipients, including DMSO.
21\. Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 years after receiving study intervention.
22\. Plans to father a child while enrolled in this study or within 3 years after receiving study intervention.
