"mini" bank of only 8 donors supplies CMV-directed T cells to diverse recipients

• Type of Material: Article
• Authors: Ifigeneia Tzannou, Texas Children's Hospital; Ayumi Watanabe, Texas Children's Hospital; Swati Naik, Texas Children's Hospital; Rachel Daum, Texas Children's Hospital; Manik Kuvalekar, Texas Children's Hospital; Kathryn Leung, Emory University; Caridad Martinez, Texas Children's Hospital; Ghadir Sasa, Texas Children's Hospital; Mengfen Wu, Baylor College of Medicine; Adrian P. Gee, Texas Children's Hospital; Robert A. Krance, Texas Children's Hospital; Stephen Gottschalk, Texas Children's Hospital; Helen E. Heslop, Texas Children's Hospital; Bilal Omer, Texas Children's Hospital
• Language: English
• Date: 2019-09-10
• Publisher: American Society of Hematology: Blood Advances
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by The American Society of Hematology.
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2019000371
• Title of Journal or Parent Work: Blood Advances
• ISSN: 2473-9529
• Volume: 3
• Issue: 17
• Start Page: 2571
• End Page: 2580
• Grant/Funding Information: B.O. was supported by an educational National Institutes of Health K12 grant at Texas Children’s Hospital.; Funds for CMVST generation and conduct of the clinical trial were provided by Viracyte.
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

Cytomegalovirus (CMV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), and standard antiviral therapies are associated with significant side effects and development of drug-resistant mutants. Adoptively transferred donor-derived CMV-specific T cells (CMVSTs) can provide an alternative treatment modality with few side effects but are not widely available due to their patient-specific nature. Here we report the establishment and use of a bank of CMVSTs derived from just 8 CMV-seropositive donors, with HLA types representing the diverse US population, as an "off-the-shelf" therapy to treat drug-refractory infections. To date, we have screened 29 patients for study participation and identified a suitable line, with ≥2 of 8 shared HLA antigens, for 28 (96.6%) patients with a median of 4 shared HLA antigens. Of these, 10 patients with persistent/refractory CMV infections or disease were eligible for treatment; a single infusion of cells produced 3 partial responses and 7 complete responses, for a cumulative response rate of 100% (95% confidence interval, 69.2-100) with no graft-versus-host disease, graft failure, or cytokine release syndrome. Potential wider use of the tested CMVSTs across transplant centers is made more feasible by our ability to produce sufficient material to generate cells for .2000 infusions from a single donor collection. Our data indicate that a "mini" bank of CMVSTs prepared from just 8 well-chosen third-party donors can supply the majority of patients with an appropriately matched line that produces safe and effective anti-CMV activity post-HSCT.