R-MVST Cells for Treatment of Viral Infections

Recipient Inclusion Criteria:

• Men and women ages 18 years or older of all ethnic groups will be eligible for thetreatment

• Patients with history of HCT or SOT who demonstrate evidence of viral reactivationand/or infection manifesting as end-organ or systemic disease due to one or more ofthe following viruses: EBV, CMV, ADV or BK virus and suboptimal response to thestandard of care therapy.

• Recurrent or Multiple Viral Infection. RVI defined as occurrence of more than oneepisode of reactivation that required intervention or symptomatic disease inrecipient of allogeneic HCT that required standard of care treatment. MVI defined asmore than one virus reactivating (defined by PCR positivity) or causing symptomaticsystemic or end-organ disease. At least one of those viral reactivations requiredstandard of care intervention. No standard of care therapy is defined for ADV andBK. Patients with multiple infections/reactivations will be eligible as long as atleast one of those viral infections meet the criterium of "refractory".

Recipient Exclusion Criteria:

• Patients with other uncontrolled infections, except for CMV, EBV, ADV or BK. Forbacterial infections, patients must be receiving definitive therapy and have nosigns of progressing infection for 72 hours prior to the day of infusion. For fungalinfections, patients must be receiving definitive systemic anti-fungal therapy andhave no signs of progressing infection for 1 week prior to R-MVST infusion.Progressing infection is defined as hemodynamic instability attributable to sepsisor new symptoms, worsening physical signs or radiographic findings attributable toinfection. Persisting fever without other signs or symptoms will not be interpretedas progressing infection

• Patients who receive corticosteroids at ≥ 0.5mg/kg prednisone or equivalent.

• Patients who received anti-thymocyte globulin (ATG, Alemtuzumab (Campath), or otherT-Cell immunosupressive monoclonal antibodies in the last 28 days.

• Patients who received methotrexate, or other antimetabolite-type immunosuppressantsthat are toxic to proliferating T cells in the last 7 days.

• Patients who received extracorporeal photopheresis within the last 28 days.

• Patients who received checkpoint inhibitor agents (e.g., nivolumab, pembrolizumab,ipilimumab) within 3 drug half-lives of the most recent dose to the infusion ofR-MVST.

• Received donor lymphocyte infusion in last 28 days.

• Evidence of GVHD ≥ grade 2

• Evidence of biopsy-proven acute rejection in SOT recipients

• Active and uncontrolled relapse of malignancy

• Patients who are pregnant, or breastfeeding.

• Female of childbearing potential, or male with a female partner of childbearingpotential, unwilling to use a highly effective method of contraception.

• Uncontrolled intercurrent illness including, but not limited to symptomaticcongestive heart failure, unstable angina pectoris, cardiac arrhythmia, orpsychiatric illness/social situations that would limit compliance with studyrequirements.

• Patients who have received investigational (IND) product within 14 days of infusionof the the R-MVST cells.

Donor inclusion and exclusion criteria will be followed as per the most current BMT SOP (Donor selection, Donor evaluation and Donor Deferral).