Adenoviral Cellular Therapy with Adenovirus (ADV)-Specific Cytotoxic T-Lymphocytes (CTLs) for Resistant Infections in Children, Adolescent, and Young Adult (CAYA) Patients Following Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT): A Promising Approach
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Le résumé fourni par la source
AlloHSCT serves as a long-term curative intervention for CAYA with varied disorders but poses risks like refractory ADV infections due to impaired T-cell immunity (George/Cairo, BJH, 2012). Here, we report data from the Viral Cytotoxic T-Lymphocyte Consortium (VIRCTLC), showing the safety and efficacy of employing familial ADV-specific CTLs in AlloHSCT recipients. Assess safety and effectiveness of familial ADV-specific CTLs for refractory ADV post-AlloHSCT. Patients post-AlloHSCT showing refractory ADV were eligible. Refractory ADV infection was defined by increasing serum RT-PCR DNA (by 1 log) after 7 days or persistent quantitative RT-PCR DNA copies after 14 days of appropriate anti-viral therapy, and/or known resistance/intolerance to anti-viral agents. Related donors were matched at ≥3 HLA (A, B, or DRB1) loci and had an adequate T-cell IFN-γ response to ADV specific MACS PepTivators®. Direct selection was used to expedite cell product generation, in a point-of-care setting. Donor peripheral blood mononuclear cells were collected using non-mobilized apheresis. ADVCTLs were isolated using the CliniMACS ® Prodigy following stimulation with specific MACS® GMP PepTivator® AdV5 Hexon, provided by Miltenyi Biotec®. ADV-specific CTLs were enriched using a Cytokine Capture System (CCS). Target cell dose was 0.5 × 104 CD3+ cells/kg (recipient weight) for haploidentical related donors and 2.5 × 104 CD3+ cells/kg for matched related donors. Repeated doses were permitted every 2 weeks in the absence of a complete response (CR) and adverse events. The following were used to define response after initial 5 doses: CR - undetected ADV PCR, partial response (PR) - at least one log decrease from baseline, progressive disease (PD) – at least one log increase from baseline, and patients with stable disease. Of 15 enrolled patients (10F, 5M; ages 1-19), all post-AlloHSCT, 8 vsCTLs were derived from the original familial HSCT donors, and 7 from third-party donors (5 maternal, 2 paternal). The mean number of ADV CTL infusions was 3.7 (range: 1-16). Thirteen patients achieved CR as defined and 2 achieved PR. The overall response (OR) was 100% and the CR was 88%. The average time to OR was 33 days (range 6-112 days). Day 100 and 365 overall survival post-HSCT was 86.1% (CI95: 49.4-95.7) and 70.5% (CI95: 38.9-87.8), respectively (Figure 1). Among CR patients, Day 100 and 365 survival was 83.9% (CI95: 55.0-94.3) and 74.6% (CI95: 39.8-91.1), respectively. ADV-related mortality at both time points was 0% (Figure 2). One patient developed acute grade 2 skin GVHD possibly related to infusion, which resolved. Preliminary data affirm that donor ADV-specific CTLs are safe and effective in treating refractory ADV cases post-AlloHSCT. Manufacturing is rapid and reliable. Supported by FDA RO1006301A1. Enrollment is ongoing.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Adenoviral Cellular Therapy with Adenovirus (ADV)-Specific Cytotoxic T-Lymphocytes (CTLs) for Resistant Infections in Children, Adolescent, and Young Adult (CAYA) Patients Following Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT): A Promising Approach
- Date Crossref
- 01/02/2024
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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New York Medical College Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Children's Hospital of Philadelphia pays non établi dans la noticeOrganisme public
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Washington University in St. Louis pays non établi dans la noticeUniversité ou école supérieure
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Nationwide Children's Hospital Hematology/Oncology/BMT pays non établi dans la noticeÉtablissement de santé
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Medical College of Wisconsin Division of Hematology and Oncology pays non établi dans la noticeUniversité ou école supérieure
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Children's Hospital Colorado Center for Cancer & Blood Disorders pays non établi dans la noticeÉtablissement de santé
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University of Colorado Denver pays non établi dans la noticeUniversité ou école supérieure
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University of California Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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UCSF Benioff Children's Hospital and Blood and Marrow Transplantation pays non établi dans la noticeÉtablissement de santé
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Sidney Kimmel Comprehensive Cancer Center pays non établi dans la noticeStructure de recherche
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Department of Pathology and Laboratory Medicine pays non établi dans la noticeStructure de recherche
Pediatrics — New York Medical College, Children's Hospital of Philadelphia et Washington University in St. Louis, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.