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, Patrick J. Hanley, Yueh-Yun Chi, Paibel Aguayo-Hiraldo, Christopher C. Dvorak, Michael R. Verneris, Donald B. Kohn, Sung-Yun Pai, Blachy J. Dávila Saldaña, Benjamin Hanisch, Troy C. Quigg, Roberta H. Adams, Ann Dahlberg, Shanmuganathan Chandrakasan, Hasibul Hasan, Jemily Malvar, Mariah A. Jensen-Wachspress, Christopher A. Lazarski, Gelina Sani, John M. Idso, Haili Lang, Pamela Chansky, Chase D. McCann, Jay Tanna, Allistair A. Abraham, Jennifer L. Webb, Abeer Shibli, Amy K. Keating, Prakash Satwani, Pawel Muranski, Erin Hall, Michael J. Eckrich, Evan Shereck, Holly Miller, Ewelina Mamcarz, Rajni Agarwal, Satiro N. Oliveira, Mark T. Lugt, Christen L. Ebens, Victor M. Aquino, Jeffrey J. Bednarski, Julia Chu, Suhag Parikh, Jennifer Whangbo, Michail Lionakis, Elias T. Zambidis, Elizabeth Gourdine, Catherine M. Bollard and Michael A. Pulsipher ()
Additional contact information
Michael D. Keller: Children’s National Hospital
Patrick J. Hanley: Children’s National Hospital
Yueh-Yun Chi: University of Southern California
Paibel Aguayo-Hiraldo: Children’s Hospital of Los Angeles
Christopher C. Dvorak: University of California San Francisco
Michael R. Verneris: Children’s Hospital Colorado and University of Colorado
Donald B. Kohn: University of California, Los Angeles
Sung-Yun Pai: National Cancer Institute
Blachy J. Dávila Saldaña: Children’s National Hospital
Benjamin Hanisch: Children’s National Hospital
Troy C. Quigg: Helen DeVos Children’s Hospital
Roberta H. Adams: Phoenix Children’s/Mayo Clinic Arizona
Ann Dahlberg: Fred Hutch Cancer Center/Seattle Children’s Hospital/University of Washington
Shanmuganathan Chandrakasan: Children’s Healthcare of Atlanta
Hasibul Hasan: Children’s Hospital of Los Angeles
Jemily Malvar: Children’s Hospital of Los Angeles
Mariah A. Jensen-Wachspress: Children’s National Hospital
Christopher A. Lazarski: Children’s National Hospital
Gelina Sani: Children’s National Hospital
John M. Idso: Children’s National Hospital
Haili Lang: Children’s National Hospital
Pamela Chansky: Children’s National Hospital
Chase D. McCann: Children’s National Hospital
Jay Tanna: Children’s National Hospital
Allistair A. Abraham: Children’s National Hospital
Jennifer L. Webb: Children’s National Hospital
Abeer Shibli: Children’s National Hospital
Amy K. Keating: Dana-Farber Cancer Institute and Boston Children’s Hospital
Prakash Satwani: Columbia University Medical Center
Pawel Muranski: Columbia University Medical Center
Erin Hall: Children’s Mercy Kansas City
Michael J. Eckrich: Wake Forest School of Medicine
Evan Shereck: Oregon Health & Science Univ
Holly Miller: Phoenix Children’s/Mayo Clinic Arizona
Ewelina Mamcarz: St. Jude Children’s Research Hospital
Rajni Agarwal: Stanford University
Satiro N. Oliveira: University of California, Los Angeles
Mark T. Lugt: University of Michigan
Christen L. Ebens: University of Minnesota MHealth Fairview Masonic Children’s Hospital
Victor M. Aquino: University of Texas, Southwestern Medical Center Dallas
Jeffrey J. Bednarski: Washington University School of Medicine
Julia Chu: University of California San Francisco
Suhag Parikh: Children’s Healthcare of Atlanta
Jennifer Whangbo: Dana Farber Institute and Boston Children’s Hospital
Michail Lionakis: National Institute of Allergy and Infectious Diseases
Elias T. Zambidis: Johns Hopkins University School of Medicine
Elizabeth Gourdine: Children’s Hospital of Los Angeles
Catherine M. Bollard: Children’s National Hospital
Michael A. Pulsipher: Spencer Fox Eccles School of Medicine at the University of Utah

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47057-2

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