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. 2016 Jun 1;22(11):2684-96.
doi: 10.1158/1078-0432.CCR-15-1527. Epub 2016 Jan 27.

The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma (V体育安卓版)

Marco Ruella  1 , Saad S Kenderian  2 , Olga Shestova  1 , Joseph A Fraietta  1 , Sohail Qayyum  3 , Qian Zhang  3 , Marcela V Maus  4 , Xiaobin Liu  3 , Selene Nunez-Cruz  1 , Michael Klichinsky  1 , Omkar U Kawalekar  1 , Michael Milone  5 , Simon F Lacey  6 , Anthony Mato  7 , Stephen J Schuster  7 , Michael Kalos  6 , Carl H June  5 , Saar Gill  8 , Mariusz A Wasik  9
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"VSports在线直播" The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma

Marco Ruella et al. Clin Cancer Res. .

Abstract

Purpose: Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner. VSports手机版.

Experimental design: MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models. V体育安卓版.

Results: MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019- as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P < 0. 005) but most mice receiving CTL019 monotherapy eventually relapsed. Therefore, we added ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 + ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P < 0. 05) V体育ios版. .

Conclusions: Combining CTL019 with ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL VSports最新版本. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684-96. ©2016 AACR. .

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