IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia Academic Article uri icon

Overview

MeSH Major

  • Antigens, CD19
  • B-Lymphocytes
  • Fetal Blood
  • Immunotherapy
  • Interleukin-12
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • T-Lymphocytes

abstract

  • Disease relapse or progression is a major cause of death following umbilical cord blood (UCB) transplantation (UCBT) in patients with high-risk, relapsed or refractory acute lymphoblastic leukemia (ALL). Adoptive transfer of donor-derived T cells modified to express a tumor-targeted chimeric antigen receptor (CAR) may eradicate persistent disease after transplantation. Such therapy has not been available to UCBT recipients, however, due to the low numbers of available UCB T cells and the limited capacity for ex vivo expansion of cytolytic cells. We have developed a novel strategy to expand UCB T cells to clinically relevant numbers in the context of exogenous cytokines. UCB-derived T cells cultured with interleukin (IL)-12 and IL-15 generated >150-fold expansion with a unique central memory/effector phenotype. Moreover, UCB T cells were modified to both express the CD19-specific CAR, 1928z, and secrete IL-12. 1928z/IL-12 UCB T cells retained a central memory-effector phenotype and had increased antitumor efficacy in vitro. Furthermore, adoptive transfer of 1928z/IL-12 UCB T cells resulted in significantly enhanced survival of CD19(+) tumor-bearing SCID-Beige mice. Clinical translation of CAR-modified UCB T cells could augment the graft-versus-leukemia effect after UCBT and thus further improve disease-free survival of transplant patients with B-cell ALL.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5189717

Digital Object Identifier (DOI)

  • 10.1038/leu.2014.215

PubMed ID

  • 25005243

Additional Document Info

start page

  • 415

end page

  • 22

volume

  • 29

number

  • 2