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Combining Adoptive Cellular and Immunocytokine Therapies to Improve Treatment of B-Lineage Malignancy

Divisions of ¹ Molecular Medicine, ² Cancer Immunotherapeutics and Tumor Immunology, ³ Biomedical Informatics, ⁴ Hematology and Hematopoietic Cell Transplantation, and ⁵ Pediatric Hematology/Oncology, Beckman Research Institute and City of Hope National Medical Center; ⁶ EMD Lexigen Research Center, Billerica, Massachusetts; and ⁷ Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Laurence J.N. Cooper, Pediatrics-Research, Unit 907, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-563-3360; Fax: 713-563-0604; E-mail: ljncooper{at}mdanderson.org.

Currently, the lineage-specific cell-surface molecules CD19 and CD20 present on many B-cell malignancies are targets for both antibody- and cell-based therapies. Coupling these two treatment modalities is predicted to improve the antitumor effect, particularly for tumors resistant to single-agent biotherapies. This can be shown using an immunocytokine, composed of a CD20-specific monoclonal antibody fused to biologically active interleukin 2 (IL-2), combined with ex vivo expanded human umbilical cord blood–derived CD8⁺ T cells, that have been genetically modified to be CD19 specific, for adoptive transfer after allogeneic hematopoietic stem-cell transplantation. We show that a benefit of targeted delivery of recombinant IL-2 by the immunocytokine to the CD19⁺CD20⁺ tumor microenvironment is improved in vivo persistence of the CD19-specific T cells, and this results in an augmented cell-mediated antitumor effect. Phase I trials are under way using anti-CD20-IL-2 immunocytokine and CD19-specific T cells as monotherapies, and our results warrant clinical trials using combination of these two immunotherapies. [Cancer Res 2007;67(6):2872–80]

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