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

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.

Keywords: Cancer immunotherapy; Costimulation; T cells; Tregs.