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

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BlankIn vitro and in vivo model of a novel immunotherapy approach for chronic

lymphocytic leukemia by anti-CD23 chimeric antigen receptor.

GM Giordano Attianese, V Marin, V Hoyos, B Savoldo, I Pizzitola, S Tettamanti, V

Agostoni, M Parma, M Ponzoni, MT Bertilaccio, P Ghia, A Biondi, G Dotti, and E

Biagi

Blood, March 15, 2011; .

Centro di Ricerca Matilde Tettamanti, Department of Pediatrics, University of

Milano-Bicocca, San Gerardo Hospital, Monza, Italy;

Chronic lymphocytic leukemia (CLL) is characterized by an accumulation of mature

CD19(+)CD5(+)CD20(dim) B lymphocytes that typically express the B-cell

activation marker CD23. Here 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, expressed

physiologically also by normal B lymphocytes. Moreover, CLL derived CD23.CAR(+)

T cells released inflammatory cytokines (1445-fold more TNF-?, 20-fold more

TNF-? and 4-fold more IFN-?). Interleukin-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(-/-)?©(-/-) xenograft mouse model. Compared with mice treated with

control T cells, the infusion of CD23.CAR(+) T cells resulted in fact in a

significant delay in growth of MEC-1 CLL cell line. Altogether these data

suggest that CD23.CAR(+) T cells represent a selective immunotherapy for the

elimination of CD23(+) leukemic cells in patients with CLL.

PMID: 21406718