AUTHOR=Santamaria Silvia , Delgado Marisa , Botas Marta , Castellano Eva , Corraliza-Gorjon Isabel , Lafuente Paloma , Muñoz-Calleja Cecilia , Toribio Maria L. , Kremer Leonor , Garcia-Sanz Jose A. 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.825635

DOI=10.3389/fimmu.2022.825635

ISSN=1664-3224

ABSTRACT=<p>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<sup>+</sup> 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<sup>+</sup> T-ALL tumor cells <italic>in vivo</italic>, 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<sup>+</sup> tumor treatment and might represent one of the first therapeutic antibodies for precision medicine on T-ALL patients.</p>