Synergistic anti‐tumor effect of glycosylphosphatidylinositol‐anchored IL‐2 and IL‐12

Abstract

GPI anchorage of cytokines represents a new approach to locally deliver high doses of cytokines without the severe adverse effects normally accompanied with systematic high-dose administration of these cytokines.

Antitumor effects of a tumor cell vaccine expressing a membrane-bound form of the IL-12 p35 subunit

“…30 To stimulate dendritic cells directly, a tumor cell vaccine expressing a membrane-bound form of GM-CSF has also been expressed on tumor cells. 31 Similarly, to compensate for missing stimulatory signals for T cell activation in tumor bearers, a number of groups have prepared tumor vaccines expressing membrane-bound forms of IL-2, [32][33][34][35][36] Antibodies and reagents. Control rat-IgG, PE-anti-IL-12p40, PE-anti-CD4, PE-anti-CD8, FITC-anti-CD69, purified anti-L-d, PE-goat anti-rat IgG, PE-rat anti-mouse IgG, and recombinant mouse IL-2 and IL-12 were purchased from BD PharMingen (San Diego, CA).…”

“…than the secreted form. [21][22][23][24][25][26][27][28][29][30][31][32][33][34] Hence in this study we investigated whether the p35 subunit of IL-12 has IL-12-like biological activity by examining the immunity induced by a clone of MethA fibrosarcoma cells expressing p35 in membrane-bound form so that it could be expressed without co-expression of p40 subunit. We found that tumor cells expressing mbIL-12p35 had reduced tumorigenicity, and induced antitumor immunity to MethA cells in a CD8 + T cell-dependent manner.…”

Cancer Immunotherapy Using a Membrane-bound Interleukin-12 With B7-1 Transmembrane and Cytoplasmic Domains

“…30 The antitumor effect of GPI-anchored IL-12 can be further enhanced by coexpression of GPI-anchored IL-2 on the same tumor cells. 34 However, whether membrane-bound IL-12 can be used to treat more clinically relevant established tumors remains unexplored and the antitumor mechanisms of membrane-bound IL-12 have yet to be defined.…”

Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma

“…The availability of cytokines on tumor cell surface can eventually bring immune cells to the tumor site for better antigen uptake and stimulation, thereby inducing antitumor effects at a higher efficiency. On the basis of these assumptions, this type of modified cytokine gene therapy has been reported on interleukin-2, 13,19,20 interleukin-12, 21 fractalkine (CX3CL1) 22 and TNF. 23 Indeed, accumulating evidence revealed that the membrane-bound form of cytokine genes can exhibit more antitumor effects than the corresponding soluble ones.…”