Adoptive transfer of autologous T cells improves T-cell repertoire diversity and long-term B-cell function in pediatric patients with neuroblastoma

Clin Cancer Res. 2012 Dec 15;18(24):6732-41. doi: 10.1158/1078-0432.CCR-12-1432. Epub 2012 Oct 23.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Antigens, Bacterial / immunology
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • Child, Preschool
  • Female
  • Humans
  • Immunologic Memory
  • Immunotherapy, Adoptive
  • Infant
  • Influenza Vaccines / immunology
  • Linear Models
  • Lymphocyte Count
  • Male
  • Neuroblastoma / immunology
  • Neuroblastoma / therapy*
  • Pilot Projects
  • Statistics, Nonparametric
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Antigens, Bacterial
  • Influenza Vaccines