Haploidentical Viral Specific Cytotoxic T-Lymphocytes (Vctls) for the Treatment of Refractory Viral Infections in Primary Immunodeficiency (Pid), Solid Organ (Sot) or Allogeneic Bmt Patients
Author Type(s)
Faculty
Document Type
Abstract
Publication Date
2022
DOI
10.1002/pbc.299522
Journal Title
Pediatric Blood and Cancer
Department
Pediatrics
Abstract
Background and Aims: Viral infections cause significant mortality in patients with immunodeficiencies. Due to limitations of antiviral therapies, adoptive immune therapy has been developed to provide T-cell immunity. Ex-vivo production of vCTLs is limited by time and quantities for infusion. Miltenyi Biotec developed the CliniMACS Prodigy which isolates virus specific CD4+/CD8+ T cells from donors after incubation with viral antigen peptides. The Multicenter Viral CTL Consortium was created to treat immunocompromised patients. To demonstrate vCTLs manufactured using the CliniMACS Prodigy for CMV, EBV, AdV, and BK virus is safe and effective for immunocompromised patients with refractory viral infections. Methods: Patients 0.1-30 years with PID or following SOT or alloHSCT with refractory viral illnesses were eligible. Unmobilized PBMCs were obtained via apheresis. vCTLs were manufactured using the CliniMACS® Prodigy. HLA mismatched related donor cells were infused at 0.5x104 CD3/kg per dose. Infusions of vCTLs Q2 weeks based on response and toxicity (maximum of 5 infusions). CR=PCR negative and PR=PCR ≥1 log decrease. Results: Thirty-three patients met eligibility with two PID and 31 alloHSCT/SOT. Donors were screened. Four patients became ineligible; n=1 due to death from a viral infection, n=1 parental refusal and n=2 subjects with decreasing viral titers. Seventeen patients received vCTLs from their original haplo BMT donor and 12 received third party haplo-related donor vCTL infusions. Seven patients received CMV CTLs, 15 ADV CTLs, 5 BK CTLs, and 2 EBV vCTLs. Of the evaluable patients, responses were 17-CR, five-PR, three-SD, and one-PD with an ORR 85%. Two of the patients developed grade II-III aGVHD of the skin. There was no extensive cGVHD, infusion reactions, or CRS related to vCTLs. Conclusions: The manufacturing of vCTLS using the CliniMACS Prodigy for patients with PID or following SOT or alloHSCT is efficient and the treatment appears safe and effective. Supported by FDA R01006363.
Recommended Citation
Talano, J., Milner, J., Harrison, L., Ayello, J., Flower, A., Chu, Y., Johnson, B., Li, Y., Lee, D., Chu, J., Dvorak, C., O'Donnell, L., Wang, Y., Bunin, N., & Cairo, M. (2022). Haploidentical Viral Specific Cytotoxic T-Lymphocytes (Vctls) for the Treatment of Refractory Viral Infections in Primary Immunodeficiency (Pid), Solid Organ (Sot) or Allogeneic Bmt Patients. Pediatric Blood and Cancer, 69, S147. https://doi.org/10.1002/pbc.299522
