Interferon-alpha gene therapy in combination with CD80 transduction reduces tumorigenicity and growth of established tumor in poorly immunogenic tumor models

Abstract

Interferon-alpha (IFN-␣) or CD80 transduction of tumor of IFN-␣ and Neo cells or CD80 and Neo cells led to tumors cells individually reduces tumorigenicity and enhances associated with progressive growth. Induction of long-lastantitumor responses. Here, we report that the combination ing tumor immunity against WT tumor cells was demonof IFN-␣ and CD80 cancer gene therapy in poorly immunostrated by rejection of a subsequent rechallenge in 10 of genic murine tumor models, the colorectal adenocarcin-13 (MC38) and six of seven (MCA205) tumor-free mice. oma cell line MC38, and the methylcholanthrene-inducedThe therapeutic efficacy with established WT MC38 tumors fibrosarcoma cell line MCA205 reduces tumor growth more was shown when mice were treated with a vaccine conefficiently without affecting in vitro growth. Wild-type (WT), sisting of repetitive injections of IFN-␣-and CD80-transneomycin-resistance (Neo) gene-, or CD80-transduced duced MC38 cells into the contralateral flank (P Ͻ 0. 01). tumor cells grew progressively in all immunocompetentThis treatment was associated with accumulation of CD4 + , mice. In contrast, IFN-␣-transduced MC38 or MCA205 CD8 + cells and dendritic cells within the established tumor, cells were rejected in 13 of 15 and seven of 15 mice, demonstrating induction of antitumor immune responses. respectively. Synergistic effects were observed when Combination gene therapy using IFN-␣ and CD80 is IFN-␣-and CD80-transduced tumor cells were mixed and an effective immune therapy of cancer and could be inoculated. These admixed cells were rejected by 14 of 15 considered for clinical trials. (MC38) or seven of 15 mice (MCA205), whereas, a mixture

Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors

“…35 The expression of IFN-a was confirmed by enzyme-linked immunosorbent assay (ELISA) using a commercially available kit according to the manufacturer's instructions (mouse IFN-a ELISA, PBL InterferonSource, New Brunswick, NJ). MC38 cells expressing the neomycin-resistance gene following retroviral transduction with MFG-Neo (MC38-Neo) were used as control cells.…”

“…MC38 cells expressing the neomycin-resistance gene following retroviral transduction with MFG-Neo (MC38-Neo) were used as control cells. 35 Gamma-irradiation (100 Gy for tumor cells) was performed with Gammacell 3000 Elan (Nordion, Kanata, ON, Canada). As reported previously, 1 Â ) were harvested from these mice on day 35 and then incubated in the presence of irradiated (100 Gy) and genetically modified MC38 (2 Â 10 5 cells ml --1 ) or 10 mg ml --1 of anti-PD-1 antagonistic antibody (BioLegend, San Diego, CA) either alone or in combination in complete medium.…”

Interleukin-4 gene transduced tumor cells promote a potent tumor-specific Th1-type response in cooperation with interferon-α transduction

“…41 In brief, B6 mice first were injected in the right flank with MC38-WT cells (1 Â 10 5 cells s.c.). Injection of 1 Â 10 5 MC38-Neo, or -IL4 cells in the contralateral (left) flank, followed three times at 3-day intervals starting at day 7, when tumors had reached a cross-sectional area of 16-30 mm 2 ( Figure 1, Experiment 2).…”

Current Immunotherapeutic Strategies for Central Nervous System Tumors

“…Antitumor effects mediated by expression of cytokines in cancer models have been demonstrated with IL-2, IL-4, IL-12, IL-23, IFN-α, and GM-CSF [33][34][35][36][37][38][39][40]. Cytokine gene therapy for malignant glioma has been investigated as a tool for enhancement of T cell activity and APC activation.…”