Immunizations With IFNγ Secreting Tumor Cells can Eliminate Fully Established and Invasive Rat Gliomas

Abstract

Immunotherapy of malignant primary brain tumors holds the potential to improve the dismal prognosis after current clinical therapy. Although immunotherapy of experimental gliomas has been demonstrated to have the capacity to cure intracerebral tumors no convincing effects of immunotherapy have been shown in clinical trials. One reason for this could be that some of the models used do not display full features of human glioblastomas. The N29 rat gliomas exhibited all the histologic features of human glioblastoma multiforme including nuclear atypia, mitotic figures, necrosis, and diffuse infiltration into the normal brain tissue. Surprisingly, immunotherapy with autologous interferon gamma producing tumor cells against preestablished intracerebral N29 tumors yielded a higher cure rate than immunotherapy against less invasive tumors. Furthermore, when immunizations were postponed until day 5 after tumor establishment 50% of the animals survived. When immunizations were postponed until day 11 after tumor establishment no glioma-bearing animals were cured but survival was significantly prolonged. The superior effect of immunotherapy in the invasive N29 model compared with the less invasive tumors could depend on combined effects of up-regulation of major histocompatibility complex I and induction of major histocompatibility complex II plus CD80 after transfection and irradiation of the tumor cells used for immunizations. This study demonstrates that immunotherapy against experimental brain tumors indeed is feasible even against highly invasive and established tumors. These results strengthen the translational potential of immunotherapy against malignant brain tumors.

Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors

“…growing experimental rat gliomas in response to peripheral immunization with irradiated interferon-γ (IFN-γ) secreting tumor cells [4,5].…”

Cellular Mechanism of Newly Synthesized Indoledione Derivative-induced Immunological Death of Tumor Cell

“…In general, IFN-γ is known to be produced by T cells or NK cells not by tumor cells. Immunotherapy with IFN-γ secreting tumor cells were proven to be effective cancer vaccine in animal model (18,19), suggesting that EY-6-manipulated IFN-γ secretion from the MC38 cells may be one of the important mechanism for inducing anti-tumor responses. Unlike the anti-tumor immune effect on the tumor cells, EY-6 did not affect normal antigen presenting cell, DC maturation or cross presentation function (Fig.…”

Intratumorally implanted mesenchymal stromal cells potentiate peripheral immunotherapy against malignant rat gliomas

“…The N32 rat glioma cell line is syngeneic with Fischer 344 rats and resembles anaplastic astrocytoma (Janelidze et al, 2009). The cells have been transduced to express IFNγ (N32-IFNγ) (Visse et al, 1999) and both cell lines were cultured as described elsewhere (Eberstal et al, 2012).…”