Preclinical activity of anti-CCR7 immunotherapy in patients with high-risk chronic lymphocytic leukemia

Cancer Immunology, Immunotherapy : CII
Carlos Cuesta-MateosCecilia Muñoz-Calleja

Abstract

Chronic lymphocytic leukemia (CLL) with deletions of the p53 locus on chromosome 17 and/or refractory to fludarabine chemoimmunotherapy remains a major clinical problem with few therapeutic options. Currently, these types of CLL are treated with approaches that do not target the p53 pathway, such as small molecules and monoclonal antibodies (mAb). We have previously postulated anti-CCR7 mAb therapy as a novel CLL treatment. In the present study, we evaluated the in vitro efficacy of anti-CCR7 mAb as a single agent in CLL patients with high-risk cytogenetics and/or refractory to fludarabine, by measuring CCR7 surface expression and complement-dependent cytotoxicity. Our results demonstrate that CCR7 is highly expressed in challenging and heavily treated CLL patients. In addition, the complement-mediated mechanism of action of this mAb effectively eradicates CLL cells while sparing subsets of T cells in these patients. Moreover, this mAb outperformed the activity of alemtuzumab, the mAb with the highest efficacy in these groups. Finally, in vitro activity was also demonstrated in patients with a disease refractory to both fludarabine and alemtuzumab, and patients harboring 11q22 deletion. Our results propose that anti-CCR7 mAb is...Continue Reading

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Citations

May 22, 2016·Diabetes·Jason HellmannMatthew Spite
Feb 2, 2018·Frontiers in Immunology·Carlos Cuesta-MateosCecilia Muñoz-Calleja
Dec 30, 2017·Molecular and Clinical Oncology·Hyewon RyuHyo Jin Lee
Feb 23, 2020·Bone Marrow Transplantation·Carlos Cuesta-MateosCecilia Muñoz-Calleja
Oct 29, 2020·Biomarker Research·Carlos Cuesta-MateosCecilia Muñoz-Calleja

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