Abstract 923: Ibrutinib inhibits malignant cell adhesion and migration and reduces tumor burden in lymph node and bone marrow in a murine model of mantle cell dissemination and progression
| Autor: | Padmaja Magadala, Joseph J. Buggy, Michelle Francesco, Lucy Jawed, Betty Chang, Stella Chang, Susanne M. Steggerda, Patricia Thiemann |
|---|---|
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:923-923 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2013-923 |
| Popis: | Introduction: Ibrutnib is a potent and selective Btk inhibitor that covalently modifies Cys481 in Btk and inhibits B cell antigen receptor (BCR) signaling. Ibrutinib is currently in a Phase II study in patients with relapsed or refractory mantle cell lymphoma (MCL). In MCL patients following 1-2 weeks of ibrutinib treatment, we observed a transient increase of MCL cells in peripheral blood which was associated with a rapid reduction of tumor burden in MCL patients suggesting mobilization of malignant cells from tissues to the periphery (Wanga; Changb). At the same time, levels of plasma chemokines CCL4, CCL22, CXCL13 were significantly decreased by 40-60% (p Results and Conclusions: Ibrutinib inhibited phosphorylation of Btk, PLCγ, Erk and JNK in MCL cell lines (Mino, Jeko, HBL2) and primary MCL cells stimulated by co-culture with stromal cells or anti-IgM. Furthermore, ibrutinib inhibited BCR- and chemokine (CXCL12, CXCL13)-induced adhesion and migration of MCL cells lines, and the migration of MCL underneath bone marrow-derived stromal cells in co-culture (pseudoemperipoleisis). In addition, ibrutinib significantly inhibited the production of chemokines CCL3, CCL4, CCL22, TARC and CXCL13 by 50-70% (p aWang L et al., ASH 2011. bChang BY et al., ASH 2011. Citation Format: Betty Y. Chang, Michelle Francesco, Susanne Steggerda, Stella Chang, Padmaja Magadala, Lucy Jawed, Patricia Thiemann, Joseph J. Buggy. Ibrutinib inhibits malignant cell adhesion and migration and reduces tumor burden in lymph node and bone marrow in a murine model of mantle cell dissemination and progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 923. doi:10.1158/1538-7445.AM2013-923 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|