T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies

Donald R. Shaffer, Barbara Savoldo, Zhongzhen Yi, Kevin K.H. Chow, Sunitha Kakarla, David M. Spencer, Gianpietro Dotti, Meng Fen Wu, Hao Liu, Shannon Kenney, Stephen Gottschalk

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81 Scopus citations

Abstract

T-cell therapy with genetically modified T cells targeting CD19 or CD20 holds promise for the immunotherapy of hematologic malignancies. These targets, however, are only present on B cell-derived malignancies, and because they are broadly expressed in the hematopoietic system, their targeting may have unwanted consequences. To expand T-cell therapies to hematologic malignancies that are not B cell-derived, we determined whether T cells can be redirected to CD70, an antigen expressed by limited subsets of normal lymphocytes and dendritic cells, but aberrantly expressed by a broad range of hematologic malignancies and some solid tumors. To generate CD70-specific T cells, we constructed a chimeric antigen receptor (CAR) consisting of the CD70 receptor (CD27) fused to the CD3-ξ chain. Stimulation of T cells expressing CD70-specific CARs resulted in CD27 costimulation and recognition of CD70-positive tumor cell lines and primary tumor cells, as shown by IFN-γ and IL-2 secretion and by tumor cell killing. Adoptively transferred CD70-specific T cells induced sustained regression of established murine xenografts. Therefore, CD70-specific T cells may be a promising immunotherapeutic approach for CD70-positive malignancies.

Original languageEnglish (US)
Pages (from-to)4304-4314
Number of pages11
JournalBlood
Volume117
Issue number16
DOIs
StatePublished - Apr 21 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Shaffer, D. R., Savoldo, B., Yi, Z., Chow, K. K. H., Kakarla, S., Spencer, D. M., Dotti, G., Wu, M. F., Liu, H., Kenney, S., & Gottschalk, S. (2011). T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. Blood, 117(16), 4304-4314. https://doi.org/10.1182/blood-2010-04-278218