Depletion of regulatory T cells by targeting folate receptor 4 enhances the potency of a GM-CSF-secreting tumor cell immunotherapy

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2013-08, Vol.148 (2), p.287-298
• Main Authors: Liang, Spencer C, Moskalenko, Marina, Van Roey, Melinda, Jooss, Karin
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibodies - immunology; Antibodies - therapeutic use; Cancer immunotherapy; Cancer Vaccines - immunology; Cell Line, Tumor; Costimulation; Female; Granulocyte-Macrophage Colony-Stimulating Factor - secretion; Humans; Immunotherapy - methods; Melanoma - prevention & control; Mice; Mice, Inbred C57BL; Neoplasms - secretion; Neoplasms - therapy; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; T cells; T-Lymphocytes, Regulatory - physiology; Tregs
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2013.05.011

Abstract In this report, a Treg-depleting anti-FR4 antibody is combined with a GM-CSF-secreting tumor cell immunotherapy (GVAX) for treatment of melanoma-bearing animals. Median survival time (MST) of animals treated with GVAX was 41 days, compared to a MST of 32 days in untreated animals. Anti-FR4 monotherapy had no effect on MST. Combination of anti-FR4 and GVAX significantly prolonged MST to 55 days, suggesting that these two agents can function cooperatively. Combination therapy increased expression of IFN-γ and granzyme B by CD8 T cells. In contrast to anti-CD25-mediated Treg depletion, administration of anti-FR4 after GVAX did not reduce efficacy, suggesting that anti-FR4 does not deplete effector cells induced by GVAX. Triple combination of a blocking CTLA4 antibody with GVAX and anti-FR4 further enhanced overall survival and reduced growth of well-established melanomas. Considered together, anti-FR4 antibody and GVAX may be a promising approach for the treatment of patients with cancer.