Pilot Study of Haploidentical Donor Adenovirus Specific T-lymphocytes to Treat Refractory Adenovirus Infections

Inclusion Criteria:

• Age 0 days to 60 years with one of the following conditions:

1. Patients who are solid organ transplantation recipients (renal, heart, lung,liver, pancreas, small bowel, multi-visceral) and are > 28 days post-transplantat the time of screening.

2. Patients with underlying malignancy who are receiving or have receivedchemotherapy within 6 months of screening.

3. Patients with known autoimmune or autoinflammatory conditions, not associatedwith a known underlying primary immunodeficiency

4. Patients who are receiving or have received systemic immunosuppressivetherapies in the 30 days prior to screening including: biologic agents,calcineurin inhibitors, mTOR inhibitors, or corticosteroid

5. Patients without known immunocompromised conditions

• And must meet at least 1 of the following criteria.

1. Documented ADV refractory infection (i.e., DNAemia detected by qualitative orquantitative PCR in the peripheral blood > 14 days or rising viral load inblood despite antiviral therapy >14 days).

2. Evidence of refractory ADV end organ disease (proven or probable as previouslydefined46, including pneumonitis, colitis, hepatitis, hemorrhagic cystitisetc.) despite antiviral therapy >14 days.

3. Medical intolerance to anti-viral therapies including renal toxicity (Cr >2)and/or bone marrow suppression (ANC <1500, Hb <10 and/or Plt <50) orgastrointestinal manifestation (grade ≥2 diarrhea), or other related organinjury.

4. At high risk for antiviral failure due to history of recurrent ADVreactivations, or recently started on increased immunosuppressants.

• Negative pregnancy test in female patients if applicable (childbearing potential)

• Written informed consent and/or signed assent line from patient, parent or legalguardian prior to any study-related procedures.

Exclusion Criteria:

• Receipt of anti-thymocyte globulin (ATG), alemtuzumab, cytoxan, or other T-celldepleting drugs or monoclonal antibodies within 28 days from enrollment

• Receiving corticosteroid (prednisone equivalent) ≥ 0.5mg/kg/day or ≥ 20mg/day at thetime of enrollment

• Recipients of allogeneic hematopoietic stem cell transplant (bone marrow, peripheralblood or umbilical cord blood)

• Evidence of uncontrolled infection (except ADV) as follows:

1. Bacterial infections - patients must be receiving definitive therapy and haveno signs of progressing infection for 72 hours prior to enrollment

2. Fungal infections - patients must be receiving definitive systemic anti-fungaltherapy and evidence of response/stabilization on therapy for 1 week prior toenrollment

3. Progressing infection is defined as hemodynamic instability attributable tosepsis, or new symptoms, worsening physical signs or radiographic findingsattributable to infection. Persisting fever without other signs or symptomswill not be interpreted as progressing infection

• Patient with poor performance status determined by Karnofsky (patients >16 years) orLansky (patients ≤16 years) score ≤30% (Table 5)

• Concomitant enrollment in another experimental clinical trial investigating thetreatment of refractory adenovirus infection(s)

• During the study, treatment with other investigational anti-adenoviral agents isprohibited until Week 12.

• If patient has been treated with CMX001 (brincidofovir, BCV) prior to ADV-VSTenrollment, BCV must be discontinued for at least 72 hours prior to ADV-VSTsinfusion for washout based on known geometric mean elimination half-life of BCV (8to 12 hours). Any medical condition which could compromise participation in thestudy according to the investigator's assessment

• Known HIV infection

• Female patient of childbearing age who is pregnant or breast-feeding or not willingto use an effective method of birth control during study treatment.

• Known hypersensitivity to iron dextran

• Patients unwilling or unable to comply with the protocol or unable to give informedconsent.

• Known human anti-mouse antibodies