Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment

Michael D. Keller, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Patrick J. Hanley, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Yueh-Yun Chi, Department of Pediatrics and Preventative Medicine, University of Southern California, Los Angeles, CA, USA.
Paibel Aguayo-Hiraldo, Cancer and blood disease institute, Children's Hospital of Los Angeles, Los Angeles, CA, USA.
Christopher C. Dvorak, Division of Pediatric Allergy, Immunology, and BMT, University of California San Francisco, San Francisco, CA, USA.
Michael R. Verneris, Department of Pediatrics and Division of Child's Cancer and Blood Disorders, Children's Hospital Colorado and University of Colorado, Denver, CO, USA.
Donald B. Kohn, Department of Microbiology, Immunology & Molecular Genetics and Department of Pediatrics David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Sung-Yun Pai, Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Blachy J. Dávila Saldaña, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Benjamin Hanisch, Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, DC, USA.
Troy C. Quigg, Pediatric Blood & Bone Marrow Transplant and Cellular Therapy, Helen DeVos Children's Hospital, Grand Rapids, MI, USA.
Roberta H. Adams, Center for Cancer and Blood Disorders, Phoenix Children's/Mayo Clinic Arizona, Phoenix, AZ, USA.
Ann Dahlberg, Clinical Research Division, Fred Hutch Cancer Center/Seattle Children's Hospital/University of Washington, Seattle, WA, USA.
Shanmuganathan Chandrakasan, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Hasibul Hasan, Cancer and blood disease institute, Children's Hospital of Los Angeles, Los Angeles, CA, USA.
Jemily Malvar, Cancer and blood disease institute, Children's Hospital of Los Angeles, Los Angeles, CA, USA.
Mariah A. Jensen-Wachspress, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Christopher A. Lazarski, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Gelina Sani, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
John M. Idso, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Haili Lang, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Pamela Chansky, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Chase D. McCann, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Jay Tanna, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Allistair A. Abraham, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Jennifer L. Webb, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Abeer Shibli, Center for Cancer & Immunology Research, Children's National Hospital, Washington, DC, USA.
Amy K. Keating, Pediatric Stem Cell Transplant, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
Prakash Satwani, Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Columbia University Medical Center, New York, NY, USA.
Pawel Muranski, Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Columbia University Medical Center, New York, NY, USA.
Erin Hall, Division of Pediatric Hematology/Oncology/Bone Marrow Transplant, Children's Mercy Kansas City, Kansas City, MO, USA.
Michael J. Eckrich, Pediatric Transplant and Cellular Therapy, Levine Children's Hospital, Wake Forest School of Medicine, Charlotte, NC, USA.

Document Type

Journal Article

Publication Date

4-18-2024

Journal

Nature communications

Volume

15

Issue

1

DOI

10.1038/s41467-024-47057-2

Abstract

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

Department

Pediatrics

Link to Full Text

Share

COinS