Third Party Viral Specific T-cells (VSTs)

Third Party Viral Specific T-cells (VSTs) for Treatment of Viral Infections in Immunocompromised Patients

The purpose of this study is to demonstrate that viral specific T-cells (a type of white blood cell) can be generated from an unrelated donor and given safely to patients with viral infections.

Viral reactivation and infection is a major cause of morbidity in immunocompromised patients (including HSCT recipients). In this study we will draw blood from unrelated (third party) donors and use the blood to generate viral specific T-cells (VSTs) with specificity for Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus (ADV), BK virus (BKV), and JC Virus. The VSTs will be infused into immunocompromised children with specific viral infections (EBV, CMV, ADV, BKV , or JC virus). Cells will be selected for infusion based on the recipient's HLA type and the viral specificity of the cells.

3rd party VSTs will be infused into immunocompromised patients who have evidence of viral infection or reactivation defined as any of the following: Blood adenovirus PCR ≥ 1,000 Blood CMV PCR ≥ 500 Blood EBV PCR ≥ 9,000 Plasma BKV PCR >1,000 Plasma JC Virus PCR > 1,000 Evidence of invasive adenovirus infection or disease, defined as the presence of adenoviral positivity by PCR or culture in one or more sites. Evidence of invasive CMV infection, eg pneumonitis, retinitis, colitis Evidence of EBV-associated lymphoproliferation (EBV-LPD) defined as proven EBV-LPD by biopsy or probable EBV-LPD defined as an elevated EBV DNA level in the blood associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation, or EBV-associated malignancies. Evidence of symptomatic BK virus infection, which may include symptomatic hemorrhagic cystitis, or BK nephropathy. Evidence of PML or other CNS infection due to JC virus.

Of the patients who had a VST culture initiated, successful production of VST cells is defined as meeting the protocol-defined release criteria.

Inclusion Criteria: Immunocompromised patient with evidence of viral infection or reactivation Age >1 day Recipients who have had a stem cell transplant must be at least 21 days after stem cell infusion Clinical status must allow tapering of steroids to < 0.5mg/kg prednisone or other steroid equivalent Must be able to receive CTL infusion in Cincinnati Informed consent obtained by PI or sub-investigator either in person or by phone Exclusion Criteria: Active acute GVHD grades II-IV Uncontrolled bacterial or fungal infection Uncontrolled relapse of malignancy Infusion of ATG or alemtuzumab within 2 weeks of VST infusion

Rubinstein JD, Zhu X, Leemhuis T, Pham G, Ray L, Emberesh S, Jodele S, Thomas S, Cancelas JA, Bollard CM, Hanley PJ, Keller MD, Grimley O, Clark D, Clark T, Lindestam Arlehamn CS, Sette A, Davies SM, Nelson AS, Grimley MS, Lutzko C. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Blood Adv. 2021 Sep 14;5(17):3309-3321. doi: 10.1182/bloodadvances.2021004456.

Nelson AS, Heyenbruch D, Rubinstein JD, Sabulski A, Jodele S, Thomas S, Lutzko C, Zhu X, Leemhuis T, Cancelas JA, Keller M, Bollard CM, Hanley PJ, Davies SM, Grimley MS. Virus-specific T-cell therapy to treat BK polyomavirus infection in bone marrow and solid organ transplant recipients. Blood Adv. 2020 Nov 24;4(22):5745-5754. doi: 10.1182/bloodadvances.2020003073.