Nature Medicine9, 279 - 286 (2003)
Published online: 10 February 2003; Corrected online: 10 February 2003 | doi:10.1038/nm827
Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15
Renier J. Brentjens1, Jean-Baptiste Latouche1, Elmer Santos1, 2, Francesc Marti5, Michael C. Gong1, Clay Lyddane1, 3, Philip D. King5, Steven Larson2, Mark Weiss1, Isabelle Rivière1, 3, 4
& Michel Sadelain1, 3, 4
1
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
2
Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
3
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
4
Department of the Gene Transfer and Somatic Cell Engineering Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
5
Department of Immunology, Hospital for Special Surgery, Weill Medical College and Graduate School of Cornell University, New York, New York, USA
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.
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