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

Authors: Brentjens, R. J.; Latouche, J. B.; Santos, E.; Marti, F.; Gong, M. C.; Lyddane, C.; King, P. D.; Larson, S.; Weiss, M.; Rivière, I.; Sadelain, M.
Article Title: Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15
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.
Keywords: survival rate; nonhuman; neoplasms; t-lymphocytes; animal cell; mouse; phenotype; animals; mice; cancer immunotherapy; bone marrow; tumor markers, biological; animal experiment; animal model; antineoplastic activity; mice, scid; tumor cells, cultured; acute lymphoblastic leukemia; b lymphocyte; gene transfer; genetic transduction; animalia; b-lymphocytes; b cell lymphoma; lymphocyte activation; recombinant fusion proteins; antigen recognition; cytotoxic t lymphocyte; adoptive transfer; cytolysis; chronic lymphatic leukemia; immunotherapy, adoptive; interleukin 15; cd19 antigen; lymphocyte antigen receptor; burkitt lymphoma; scid mouse; antigens, cd19; b7 antigen; tomography, emission-computed; tumor cell destruction; antigens, cd80; interleukin-15; humans; priority journal; article
Journal Title: Nature Medicine
Volume: 9
Issue: 3
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2003-03-01
Start Page: 279
End Page: 286
Language: English
DOI: 10.1038/nm827
PUBMED: 12579196
PROVIDER: scopus
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Renier J Brentjens
    189 Brentjens
  2. Elmer B Santos
    25 Santos
  3. Michel W J Sadelain
    453 Sadelain
  4. Isabelle C Riviere
    161 Riviere
  5. Steven M Larson
    764 Larson
  6. Mark Weiss
    80 Weiss
  7. Michael Gong
    8 Gong
  8. Clay   Lyddane
    10 Lyddane