In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor

Greta Maria Paola Giordano Attianese, Virna Marin, Valentina Hoyos, Barbara Savoldo, Irene Pizzitola, Sarah Tettamanti, Valentina Agostoni, Matteo Parma, Maurilio Ponzoni, Maria T S Bertilaccio, Paolo Ghia, Andrea Biondi, Gianpietro Dotti, Ettore Biagi

Research output: Contribution to journalArticle

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Abstract

Chronic lymphocytic leukemia (CLL) is characterized by an accumulation of mature CD19+CD5+CD20dim B lymphocytes that typically express the B-cell activation marker CD23. In the present study, we cloned and expressed in T lymphocytes a novel chimeric antigen receptor (CAR) targeting the CD23 antigen (CD23.CAR). CD23.CAR+ T cells showed specific cytotoxic activity against CD23+ tumor cell lines (average lysis 42%) and primary CD23+ CLL cells (average lysis 58%). This effect was obtained without significant toxicity against normal B lymphocytes, in contrast to CARs targeting CD19 or CD20 antigens, which are also expressed physiologically by normal B lymphocytes. Moreover, CLL-derived CD23.CAR + T cells released inflammatory cytokines (1445-fold more TNF-β, 20-fold more TNF-α, and 4-fold more IFN-γ). IL-2 was also produced (average release 2681 pg/mL) and sustained the antigen-dependent proliferation of CD23.CAR+ T cells. Redirected T cells were also effective in vivo in a CLL Rag2-/-γc-/- xenograft mouse model. Compared with mice treated with control T cells, the infusion of CD23.CAR+ T cells resulted in a significant delay in the growth of the MEC-1 CLL cell line. These data suggest that CD23.CAR+ T cells represent a selective immunotherapy for the elimination of CD23+ leukemic cells in patients with CLL.

Original languageEnglish
Pages (from-to)4736-4745
Number of pages10
JournalBlood
Volume117
Issue number18
DOIs
Publication statusPublished - May 5 2011

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IgE Receptors
Antigen Receptors
B-Cell Chronic Lymphocytic Leukemia
T-Cell Antigen Receptor
Immunotherapy
T-cells
Lymphocytes
B-Lymphocytes
Cells
T-Lymphocytes
CD19 Antigens
CD20 Antigens
Heterografts
Interleukin-2
Toxicity
Tumors
Tumor Cell Line
Chemical activation
In Vitro Techniques
Cytokines

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Attianese, G. M. P. G., Marin, V., Hoyos, V., Savoldo, B., Pizzitola, I., Tettamanti, S., ... Biagi, E. (2011). In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor. Blood, 117(18), 4736-4745. https://doi.org/10.1182/blood-2010-10-311845

In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor. / Attianese, Greta Maria Paola Giordano; Marin, Virna; Hoyos, Valentina; Savoldo, Barbara; Pizzitola, Irene; Tettamanti, Sarah; Agostoni, Valentina; Parma, Matteo; Ponzoni, Maurilio; Bertilaccio, Maria T S; Ghia, Paolo; Biondi, Andrea; Dotti, Gianpietro; Biagi, Ettore.

In: Blood, Vol. 117, No. 18, 05.05.2011, p. 4736-4745.

Research output: Contribution to journalArticle

Attianese, GMPG, Marin, V, Hoyos, V, Savoldo, B, Pizzitola, I, Tettamanti, S, Agostoni, V, Parma, M, Ponzoni, M, Bertilaccio, MTS, Ghia, P, Biondi, A, Dotti, G & Biagi, E 2011, 'In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor', Blood, vol. 117, no. 18, pp. 4736-4745. https://doi.org/10.1182/blood-2010-10-311845
Attianese, Greta Maria Paola Giordano ; Marin, Virna ; Hoyos, Valentina ; Savoldo, Barbara ; Pizzitola, Irene ; Tettamanti, Sarah ; Agostoni, Valentina ; Parma, Matteo ; Ponzoni, Maurilio ; Bertilaccio, Maria T S ; Ghia, Paolo ; Biondi, Andrea ; Dotti, Gianpietro ; Biagi, Ettore. / In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor. In: Blood. 2011 ; Vol. 117, No. 18. pp. 4736-4745.
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