Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma

Abstract Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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. Clin Cancer Res; 18(24); 6732–41. ©2012 AACR.</jats:p

Supplemental Data 1 from Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma

Detailed flow cytometric analysis of expanded cells from children and adults</p

Supplementary Data 3 from Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma

PDF file - 209K, B cell maturation was defined by flow cytometry</p

Supplementary Data 2 from Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma

PDF file - 435K, Representative flow cytometry plots</p

Supplemental Data 2 from Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma

Representative flow cytometry plots</p

Supplemental Data 3 from Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma

B cell maturation was defined by flow cytometry</p

Supplementary Data 1 from Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma

PDF file - 405K, Detailed flow cytometric analysis of expanded cells from children and adults</p