Therapeutic potential of an anti-CCR9 mAb evidenced in xenografts of human CCR9+ tumors

• DOI: 10.3389/fimmu.2022.825635
• Publication Date: 2022-07-27T04:35:25Z
• Authors: Silvia Santamaria; Marisa Delgado; Marta Botas; Eva Castellano; Isabel Corraliza-...; Paloma Lafuente; Cecilia Muñoz-Cal...; Maria L. Toribio; Leonor Kremer; Jose A. Garcia-Sanz
• Keywords: combined chemotherapy and immunotherapy; 0301 basic medicine; Combined chemotherapy and immunotherapy; Medicina; Immunology; Antitumoral activity; therapeutic antibodies; Adenocarcinoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; chemokine receptor CCR9; Mice; Receptors, CCR; 03 medical and health sciences; orthotopic xenograft mouse model; Animals; Humans; Chemokine receptor CCR9; antitumoral activity; Therapeutic antibodies; CCR9 positive T-ALL leukemia; Orthotopic xenograft mouse model; RC581-607; 3. Good health; Pancreatic Neoplasms; Heterografts; T-ALL leukemia; Immunologic diseases. Allergy

Relapsed or refractory T acute lymphoblastic leukemia (T-ALL) still carries poor prognosis. Aiming to improve outcomes, the therapeutic potential of an anti-CCR9 monoclonal antibody (mAb 92R), targeting the human chemokine-receptor CCR9 is analyzed on orthotopic xenotransplants. 92R mAb treatment of mice carrying human CCR9+T-ALL cell lines or primary T cell leukemias inhibits tumor growth and increases survival. The therapeutic effects of 92R are specific and synergize with chemotherapeutic agents increasing survival. Furthermore, 92R decreases size of non-hematopoietic tumors with a forced CCR9 expression and of solid tumors generated by the pancreatic adenocarcinoma cell line AsPC-1. In addition, a humanized version of 92R mAb (Srb1) is also able to inhibit growth of CCR9+T-ALL tumor cellsin vivo, increasing survival 2.66-fold. Finally, 92R mAb prevents liver accumulation of infiltrates and reduces tumor cell numbers in already formed infiltrates. Thus, the humanized version of 92R mAb (Srb1), displays therapeutic potential for CCR9+tumor treatment and might represent one of the first therapeutic antibodies for precision medicine on T-ALL patients.