Abstract 2686: Anti-tumor effects of a folate-immunoglobulin conjugate are enhanced by cytokine treatment in vitro and in vivo

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Folate conjugation is a means of selectively targeting therapeutics to folate receptor (FR)-expressing cancer cells. A novel folate-bound immunoglobulin (F-IgG) was tested for its ability to target natural killer (NK) cells to folate-receptor expressing cancer cells in the presence or absence of NK-activating cytokines. FR expression by the KB and HeLa cell lines was confirmed by immunoblot analysis (IB) and flow cytometry. Binding of F-IgG to NK cell Fc receptors led to increased phosphorylation of the epidermal growth factor related kinase (ERK) as measured by IB. Lysis of FR+ KB tumor cells by NK cells was increased 8-fold following treatment with F-IgG as compared to C-IgG (p<0.0001 across E:T ratios from 6.25:1 to 50:1). NK cell lysis of F-IgG- coated KB target cells was significantly enhanced following treatment of NK cells with IL-2, IL-12, IL-15 and IL-21 (all at 10ng/mL). NK cell production of IFN-γ, RANTES and MIP-1α was significantly enhanced by IL-12 in response to F-IgG-coated KB target cells as compared to control-treated cells (p<0.005; IFN-γ-2100 vs. 1000pg/mL, RANTES-800 vs. 150pg/mL, MIP-1α 1800 vs. 500pg/mL, respectively). Studies using the L1210JF murine leukemia model confirmed the anti-tumor activity of F-IgG and the ability of NK-activating cytokines to significantly enhance its effects. NK cell depletion in tumor-bearing mice demonstrated that the anti-tumor effects of IL-12 and F-IgG are dependent on NK cells. These studies indicate that F-IgG induces an immune response by NK cells against FR-positive cancer cell lines and that cytokine treatment has a synergistic effect on this response both in vitro and in vivo. Thus F-IgG has a potential to be used as a therapeutic antibody for the treatment of FR-positive cancers in combination with immune modulatory cytokines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2686. doi:10.1158/1538-7445.AM2011-2686