Radiation therapy improves CAR T cell activity in acute lymphoblastic leukemia

Mayumi Sugita, Takahiro Yamazaki, Mohammad Alhomoud, Jérémie Martinet, Jean Baptiste Latouche, Encouse Golden, Olivier Boyer, Koen Van Besien, Silvia C. Formenti, Lorenzo Galluzzi, Monica L. Guzman

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved for the treatment of various CD19+ hematological malignancies. While CAR T cells induce objective responses in a majority of patients, relapse frequently occurs upon loss of CD19 expression by neoplastic cells. Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer. At least in part, this reflects the ability of RT to elicit death receptor (DR) expression by malignant cells, enabling at least some degree of CAR-independent tumor killing. In a human model of CD19+ acute lymphoblastic leukemia (ALL), we also observed DR upregulation by RT, both in vitro and in vivo. Moreover, low-dose total body irradiation (LD-TBI) delivered to ALL-bearing mice prior to CAR T cell infusion considerably extended the overall survival benefit afforded by CAR T cells alone. Such an improved therapeutic activity was accompanied by a superior expansion of CAR T cells in vivo. These data encourage the initiation of clinical trials combining LD-TBI with CAR T cells in patients with hematological malignancies.

Original languageEnglish
Article number305
Pages (from-to)305
JournalCell Death and Disease
Volume14
Issue number5
DOIs
StatePublished - May 2023
Externally publishedYes

Keywords

  • Animals
  • Hematologic Neoplasms
  • Humans
  • Immunotherapy, Adoptive
  • Mice
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • T-Lymphocytes

Fingerprint

Dive into the research topics of 'Radiation therapy improves CAR T cell activity in acute lymphoblastic leukemia'. Together they form a unique fingerprint.

Cite this