Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15

Renier J. Brentjens, Jean Baptiste Latouche, Elmer Santos, Francesc Marti, Michael C. Gong, Clay Lyddane, Philip D. King, Steven Larson, Mark Weiss, Isabelle Rivière, Michel Sadelain

Research output: Contribution to journalArticlepeer-review

541 Scopus citations

Abstract

The genetic transfer of antigen receptors provides a means to rapidly generate autologous tumor-reactive T lymphocytes. However, recognition of tumor antigens by cytotoxic T cells is only one step towards effective cancer immunotherapy. Other crucial biological prerequisites must be fulfilled to expand tumor-reactive T cells that retain a functional phenotype, including in vivo cytolytic activity and the ability to travel to tumor sites without prematurely succumbing to apoptosis. We show that these requirements are met by expanding peripheral blood T cells genetically targeted to the CD19 antigen in the presence of CD80 and interleukin-15 (IL-15). T cells expanded in the presence of IL-15 uniquely persist in tumor-bearing severe combined immunodeficiency (SCID)-Beige mice and eradicate disseminated intramedullary tumors. Their anti-tumor activity is further enhanced by in vivo co-stimulation. In addition, transduced T cells from patients with chronic lymphocytic leukemia (CLL) effectively lyse autologous tumor cells. These findings strongly support the clinical feasibility of this therapeutic strategy.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalNature Medicine
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2003

Bibliographical note

Funding Information:
Acknowledgments This work was supported by US National Institutes of Health grants CA-59350, CA-86438, CA-08748, CA-83084 and AI44926; the Translational and Integrative Medicine Research Fund at the Memorial Sloan-Kettering Cancer Center; the Lymphoma Research Foundation (formerly the Cure for Lymphoma Foundation; fellowship award to R.J.B.); the Goodwin ETC fund; Golfers Against Cancer; and US Department of Energy grant ER-62039.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)

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