Effect of ibrutinib on CCR7 expression and functionality in chronic lymphocytic leukemia and its implication for the activity of CAP-100, a novel therapeutic anti-CCR7 antibody. Mateu-Albero T, Juárez-Sánchez R, Loscertales J, Mol W, Terrón F, Muñoz-Calleja C, Cuesta-Mateos C. Of Lymph Nodes and CLL Cells: Deciphering the Role of CCR7 in the Pathogenesis of CLL and Understanding Its Potential as Therapeutic Target. PublicationsĬuesta-Mateos C, Brown JR, Terrón F, Muñoz-Calleja C. The results validated CAP-100 as a novel therapeutic tool to prevent the access of CLL cells, and other neoplasia with nodal-dependence, into the LN niches, thus hitting a central hub in the pathogenesis of cancer. Additionally, CAP-100 showed a favorable toxicity profile on relevant hematopoietic subsets. Moreover, it triggered potent tumor cell killing, mediated by host immune mechanisms, and was effective in xenograft models of high-risk disease. In various in vitro and in vivo preclinical models CAP-100 strongly inhibited CCR7-induced migration, extravasation, homing, and survival in CLL and NHL samples. This means that this humanized IgG1 monoclonal antibody can not only be used as a monotherapy, but has the potential to be combined with current standards of care for CLL and other hematological malignancies. Furthermore, CAP-100 may also be an effective treatment for other CCR7-expressing B- and T-cell leukemias and lymphomas as well as for graft-versus-host disease (GvHd).īlocking tumor cell migration to the lymph nodes together with potent tumor cell killing is CAP-100’s unique mechanisms of action, which is complementary to current standard treatments for hematological malignancies. In addition, CAP-100 provides strong cell killing (ADCC) while preserving normal blood cells and inhibition of survival of tumor cells in the lymph nodes. Preclinical studies have demonstrated CAP-100’s unique ability to treat primary tumor cells from patients with human chronic lymphocytic leukemia (CLL) and different non-Hodgkin lymphoma s(NHL) at a fundamental point, by interrupting tumor cell migration to and survival in lymph nodes. CAP-100 is an anti-CCR7 antibody with a unique and biologically independent therapeutic mechanism of action for treatment of CCR7-positive hematological malignancies.
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