Detalle Publicación

ARTÍCULO
Targeting the anion exchanger 2 with specific peptides as a new therapeutic approach in B lymphoid neoplasms
Título de la revista: HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
ISSN: 0390-6078
Volumen: 103
Número: 6
Páginas: 1065 - 1072
Fecha de publicación: 2017
Resumen:
Regulatory T (Treg) cells can weaken antitumor immune responses, and inhibition of their function appears as a promising immunotherapeuticimmunotherapy therapeutic approach in cancer patients. Mice with targeted deletion of the gene encoding the Cl-HCO3-anion exchanger AE2 (also termed SLC4A2), a membrane-bound carrier involved in intracellular pH regulation, showed a progressive decrease in the number of Treg cells. We therefore challenged AE2 as a potential target for tumor immune therapy, and generated linear peptides designed to bind the third extracellular loop of AE2, which is crucial for its exchange activity. Peptide p17AE2 exhibited optimal interaction ability and indeed promoted apoptosis in mouse and human Treg cells, while activating effector T-cell function. Interestingly, this linear peptide also induced apoptosis in different types of human B-cell leukemia, lymphoma and multiple myeloma cell lines and primary malignant samples, while it showed only moderate effects on normal B lymphocytes. Finally, a macrocyclic peptide exhibiting increased stability in vivo was effective in mice xenografted with B-cell lymphoma. These data suggest that targeting the anion exchanger AE2 with specific peptides may represent an effective therapeutic approach in B-cell malignancies