Evaluation of the novel therapeutic anti‐CCR7 antibody CAP‐100 as an add‐on therapy in chronic lymphocytic leukemia patients receiving venetoclax

• Published in: Hematological oncology Vol. 41; no. 5; pp. 869 - 876
• Main Authors: Mateu‐Albero, Tamara, Marcos‐Jimenez, Ana, Delgado‐Wicke, Pablo, Terrón, Fernando, Loscertales, Javier, López‐Matencio, José María Serra, Muñoz‐Calleja, Cecilia, Cuesta‐Mateos, Carlos
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2023
• Subjects: Antibodies; antibody; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; BCL‐2; Bruton's tyrosine kinase; CAP‐100; CC chemokine receptors; CCR7; Chemokine receptors; Chronic lymphocytic leukemia; CLL; Cytotoxicity; Deregulation; Flow cytometry; Health services; Humans; Kinases; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphoma; Patients; Protein-tyrosine kinase; Receptors, CCR7 - therapeutic use; Recurrence; Therapy; Tyrosine; venetoclax; BCL-2; CLL; CCR7; antibody; venetoclax; CAP-100
• DOI: 10.1002/hon.3213
• ISSN: 0278-0232

The Bruton's tyrosine kinase inhibitor ibrutinib and the B‐cell lymphoma 2 anti‐apoptotic protein inhibitor venetoclax provide high response rates in chronic lymphocytic leukemia (CLL). However, there is a growing number of patients that relapse after treatment or show refractory disease, thus new targets and agents are still needed. We have previously reported the chemokine receptor CCR7 as a relevant deregulated target in CLL and have developed CAP‐100, a novel therapeutic anti‐CCR7 antibody that is under evaluation for relapse/refractory CLL (NCT04704323). While CCR7 expression has been shown to be down‐modulated in CLL patients treated with ibrutinib, whether venetoclax acts in a similar manner remains unaddressed. Here, we aimed to document the impact of venetoclax on CCR7 expression in CLL cells, as well as on the pre‐clinical activity of CAP‐100. To this end, we addressed CCR7 expression by flow cytometry and the antibody efficacy by means of in vitro chemotactic and antibody‐dependent cell‐mediated cytotoxicity (ADCC) assays. Our data indicate that venetoclax treatment did not significantly modify CCR7 expression pattern nor CAP‐100 mechanisms of action. Together, these findings support CAP‐100 as an adjuvant therapy to venetoclax that may introduce additional modes of action in CLL therapy.