Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells

Abstract

We investigated the antitumor effects induced by the production of interleukin-12 (IL-12) or IL-18, which influence the function of T helper type 1 cells, in murine colon carcinoma cells (Colon 26). Retrovirally transduced cells with IL-12 genes that encoded both p35 and p40 (Colon 26/IL-12) lost their tumorigenicity when inoculated subcutaneously or intraperitoneally into syngeneic immunocompetent mice. Moreover, the mice that had rejected the Colon 26/IL-12 cells generated protective immunity to wild-type

In vivo electroporation-mediated transfer of interleukin-12 and interleukin-18 genes induces significant antitumor effects against melanoma in mice

“…1 Osaki et al 18 reported a synergistic antitumor effect of IL-18 gene transduction and recombinant IL-12 administration. However, most of these earlier studies employed retrovirus, [18][19][20][21] or adenovirus vectors, 22,23 while cationic liposome was also used in some studies. 24 In the present study, IL-12 and IL-18 genes were trans-ferred into B16 solid tumors via electroporation, as a novel approach to gene therapy of cancer.…”

Intratumoral IL-18 gene transfer improves therapeutic efficacy of antibody-targeted superantigen in established murine melanoma

“…[21][22][23][24] IL-18 was shown to induce the immune defense against tumors in various animal models. [25][26][27] We hypothesized that transfection of IL-18 gene into the tumor may augment the production of tumor-suppressive cytokines (IFN-␥ and IL-2), rescue the CTL against the tumor cells, enhance NK cell activity, and thus profoundly potentiate Fab-SEA-based cancer immunotherapy.…”

The secreted form of the p40 subunit of interleukin (IL)‐12 inhibits IL‐23 functions and abrogates IL‐23‐mediated antitumour effects

“…20,21 The p19 and p35 genes were linked to the p40 gene using an internal ribosomal entry site (IRES) to construct an expression vector with pcDNA3 (Invitrogen, Carlsbad, CA): for IL-12, p35-IRES-p40; for IL-23, p19-IRES-p40; and for p40, IRES-p40. COS-7 cells were transfected with these vectors using Lipofectin reagent (Invitrogen) and cell-free supernatants were collected after 48 hr.…”