title: Adoptive transfer of autologous T cells improves T-cell repertoire diversity and long-term B-cell function in pediatric patients with neuroblastoma.
abstract: Children with high-risk neuroblastoma have a poor prognosis with chemotherapy alone, and hematopoietic stem cell transplantation offers improved survival. As a dose-escalation strategy, tandem transplants have been used, but are associated with persistent immunocompromise. This study evaluated the provision of an autologous costimulated, activated T-cell product to support immunologic function.
  
  
  
  Nineteen subjects with high-risk neuroblastoma were enrolled in a pilot phase and 23 subjects were entered in to the randomized study. Immunologic reconstitution was defined by flow cytometric and functional assays. Next-generation sequencing was conducted to identify changes to the T-cell repertoire. Twenty-two patients were vaccinated to define effects on antibody responses.
  
  
  
  Subjects who received their autologous costimulated T-cell product on day 2 had significantly superior T-cell counts and T-cell proliferation compared with those who received T cells on day 90. Early administration of autologous T cells suppressed oligoclonality and enhanced repertoire diversity. The subjects who received the day 2 T-cell product also had better responses to the pneumococcal vaccine.
  
  
  
  The infusion of activated T cells can improve immunologic function especially when given early after transplant. This study showed the benefit of providing cell therapies during periods of maximum lymphopenia.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
authors.forename: Eline Luning
authors.initials: EL
authors.lastname: Prak
authors.forename: Jean
authors.initials: J
authors.lastname: Boyer
authors.forename: Kenyetta R
authors.initials: KR
authors.lastname: McDonald
authors.forename: Suzanne
authors.initials: S
authors.lastname: Shusterman
authors.forename: Edward
authors.initials: E
authors.lastname: Thompson
authors.forename: Colleen
authors.initials: C
authors.lastname: Callahan
authors.forename: Abbas F
authors.initials: AF
authors.lastname: Jawad
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D019264:Adoptive Transfer; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D007223:Infant; D007252:Influenza Vaccines / Q000276:immunology; D016014:Linear Models; D018655:Lymphocyte Count; D008297:Male; D009447:Neuroblastoma / Q000276:immunology / Q000628:therapy*; D010865:Pilot Projects; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000942:Antigens, Bacterial; D007252:Influenza Vaccines