Treating Children, Adolescents, and Young Adults (CAYA) with Refractory Viral Infections in Primary Immunodeficiencies (PID), or Post Solid Organ Transplant (SOT) or Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT) with Virus Specific TLymphocytes (vCTLs)
Author Type(s)
Faculty
Document Type
Abstract
Publication Date
2022
DOI
10.1002/pbc.29735
Journal Title
Pediatric Blood and Cancer
Department
Pediatrics
Abstract
Background: Patients with PID and secondary immunodeficiency (SID) following SOT or AlloHSCT have compromised T-cell mediated viral immunity leading to increase in morbidity and mortality due to viral reactivation. Due to limitations of antiviral therapy, further research has gone into the development of virus-specific cytotoxic T-lymphocytes (vCTLs) (Bollard Blood 2016). Multiple studies have demonstrated efficacy and safety utilizing the IFN-γ Cytokine Capture System (CCS) using the fully automated CliniMACS Prodigy® device (Miltenyi Biotec) for isolating vCTLs as prophylactic/preemptive treatment or for treating refractory infections (Feuchtinger Blood 2010). We created a multicenter viral CTL consortium (VIRCTLC) to treat immunodeficiency patients with vCTLs and have previously demonstrated the safety and efficacy of vCTLs in this population (Flower/Cairo et al, ASTCT 2020). Objective: To demonstrate the use of Cytomeglovirus (CMV), Epstein Barr virus (EBV), adenovirus (AdV), and BK virus CTLs manufactured utilizing the CliniMACS Prodigy will be safe and effective in decreasing viral loads in CAYA PID or SID patients with refractory viral infections. Design/Methods:A phase II prospective, multicenter, multidisciplinary clinical trial under IND 17449. CAYA patients with refractory viral infections (CMV, AdV, EBV, or BK virus) who met eligibility were consented onto study. Parental donors' peripheral blood mononuclear cells were collected via non-stimulated apheresis. The vCTLs were isolated in the fully-automated IFN-γ CCS by the CliniMACS® Prodigy after incubation with MACS GMP PepTivator® peptide pools. Cell doses were limited to 0.5x104 CD3/kg in HLA mismatched related donors. vCTLs infusions were given every 2 weeks based on responses, for a maximum of 5 infusions. Results: Twenty-six patients received vCTLs. Two patients had PID, three patients were SOT recipients, and twenty-one were alloHSCT recipients. Six patients received CMV CTL infusions, 14 received ADV CTLs, three received EBV virus CTLs, and five patients received BK vCTLs. Median number of vCTL infusions was 2 (1-5). Sixteen patients (62%) achieved complete remission (CR) (PCR negative), five achieved partial response (PR) (PCR ≥1 log decrease), three had stable disease (SD), one had progressive disease (PD), one patient died prior to evaluation secondary to multiorgan system failure. No patient has developed grade III/IV acute GVHD, extensive chronic GVHD, an infusion reaction, cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome secondary to vCTLs. Conclusion: Viral specific CTLs are safe in CAYA patients with refractory viral reactivation and manufacturing via the automated CliniMACS Prodigy is reproducible in a timely manner. Accrual is ongoing.
Recommended Citation
Milner, J., Talano, J. A., Harrison, L., Ayello, J., Flower, A., Chu, Y., Rigot, O., Johnson, B. D., Li, Y., Lee, D. A., Abu-Arja, R., Chu, J., Dvorak, C. C., O'Donnell, L. C., Wang, Y., Bunin, N. J., & Cairo, M. S. (2022). Treating Children, Adolescents, and Young Adults (CAYA) with Refractory Viral Infections in Primary Immunodeficiencies (PID), or Post Solid Organ Transplant (SOT) or Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT) with Virus Specific TLymphocytes (vCTLs). Pediatric Blood and Cancer, 69 (Suppl. 2), S217-S218. https://doi.org/10.1002/pbc.29735
