Systemic interleukin 12 displays anti-tumour activity in the mouse central nervous system

Kishima, Haruhiko; Shimizu, Katsuji; Miyao, Yasuyoshi; Mabuchi, Eiichiro; Tamura, K; Tamura, Masakazu; Sasaki, Motomasa; Hakakawa, T

doi:10.1038/bjc.1998.513

Cited by 21 publications

(11 citation statements)

References 48 publications

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“…40 I.p. administration of IL-12 also induced effective antitumor immune responses against malignant glioma 60 and 4T1 mammary carcinoma. 61 Apart from direct effects on primary tumors, IL-12 was also able to eradicate lung metastasis when mammary tumors were surgically removed.…”

Section: Therapeutic Effects Of Il-12 In Preclinical Modelsmentioning

confidence: 92%

New insights into IL-12-mediated tumor suppression

et al. 2014

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During the past two decades, interleukin-12 (IL-12) has emerged as one of the most potent cytokines in mediating antitumor activity in a variety of preclinical models. Through pleiotropic effects on different immune cells that form the tumor microenvironment, IL-12 establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines depending on the type of tumor or the affected tissue. The robust antitumor response exerted by IL-12, however, has not yet been successfully translated into the clinics. The majority of clinical trials involving treatment with IL-12 failed to show sustained antitumor responses and were associated to toxic side effects. Here we discuss the therapeutic effects of IL-12 from preclinical to clinical studies, and will highlight promising strategies to take advantage of the antitumor activity of IL-12 while limiting adverse effects.

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Section: Therapeutic Effects Of Il-12 In Preclinical Modelsmentioning

confidence: 92%

New insights into IL-12-mediated tumor suppression

et al. 2014

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“…It is produced by antigen-presenting cells, including B lymphocytes, dendritic cells, and monocytes. It acts to enhance the cytolytic activity of natural killer cells and cytotoxic T lymphocytes as well as the development of a T H -1-type immune response (20)(21)(22)(23)(24)(25)(26). IL-12 also possesses antiangiogenic properties, which may represent a second potential mechanism for its antitumor activity (27,28).…”

mentioning

confidence: 99%

Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors

Gillespie

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

308

281

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“…One of these studies also addressed local intracranial administration of recombinant IL -12 using five daily intrathecal doses. 20 Minimal regression of tumor growth was seen with locally administered cytokine. This was likely a function of the extremely short in vivo half -life of recombinant IL -12 and the resultant inadequacy of the intrathecal dosing.…”

Section: Discussionmentioning

confidence: 99%

“…Kishima et al, 20 Joki et al, 21 and Kikuchi et al 22 established significantly improved survival in murine brain tumor models treated with systemically administered recombinant IL -12. Systemic IL-12 therapy was combined with either IL -2-secreting 22 or B7 -1-and ICAM -1-expressing 21 tumor cells with the aim of enhancing intratumoral antigen presentation.…”

Section: Discussionmentioning

confidence: 99%

In situ adenoviral interleukin 12 gene transfer confers potent and long-lasting cytotoxic immunity in glioma

et al. 2002

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Interleukin 12 ( IL -12 ) is a cytokine that promotes an antitumor Th1 -type pattern of differentiation in mature naïve T cells. Despite its therapeutic success in multiple animal models of cancer, the utility of systemically administered recombinant cytokine has been limited by its toxicity. This has encouraged the development of local IL -12 delivery systems through gene transfer. To determine the effect of local adenoviral delivery of IL -12 on glioma immunogenicity, mice bearing GL -26 gliomas in the right corpus striatum were treated with direct intratumoral administration of AdmIL -12, AdLacZ, or normal saline. Survival was significantly prolonged in AdmIL -12 -treated animals and immunohistochemistry demonstrated robust CD4 + and CD8 + T -cell infiltration in these mice compared to the two control groups. Glioma -infiltrating T lymphocytes from mice that received AdmIL -12 also demonstrated relatively increased, albeit statistically nonsignificant tumor killing. Based on IL -12's known ability to enhance Th1 -type cytotoxic antitumor immune responses, we postulate our findings to be a result of localized induction of tumor immunity.

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Systemic interleukin 12 displays anti-tumour activity in the mouse central nervous system

Cited by 21 publications

References 48 publications

New insights into IL-12-mediated tumor suppression

New insights into IL-12-mediated tumor suppression

Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors

In situ adenoviral interleukin 12 gene transfer confers potent and long-lasting cytotoxic immunity in glioma

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