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Titolo:
Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy
Autore:
Lohr, F; Hu, K; Haroon, Z; Samulski, TV; Huang, Q; Beaty, J; Dewhirst, MW; Li, CY;
Indirizzi:
Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 tr, Dept Radiat Oncol, Durham, NC 27710 USA Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 iv, Med Ctr, Dept Med, Durham, NC 27710 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 3, volume: 2, anno: 2000,
pagine: 195 - 203
SICI:
1525-0016(200009)2:3<195:CTOMTB>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE-THERAPY; IN-VIVO; INTERFERON-GAMMA; DENDRITIC CELLS; T-CELLS; INTERLEUKIN-12; ANTITUMOR; CANCER; IMMUNITY; INDUCE;
Keywords:
interleukin 12; IL12; costimulatory molecules; radiotherapy; immunotherapy; multimodality therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Li, CY Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3455, Durham, NC 27710 USA Duke Univ Box 3455 Durham NC USA 27710 x 3455, Durham, NC 27710 USA
Citazione:
F. Lohr et al., "Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy", MOL THER, 2(3), 2000, pp. 195-203

Abstract

Failure of local tumor control still poses a problem for radiotherapy and translates into reduced survival. Combining radiation with chemotherapy or other newer modalities has shown promising results. Immunological approaches to tumor therapy have found renewed interest due to improved insight intomechanisms involved in the immune response to tumors. In this paper, we studied tumor growth delay after various combination regimens of locally injected adenovirus constitutively expressing IL12 and B7.1 (AdIL12/B7.1) and fractionated radiotherapy in two nonimmunogenic murine tumor models, 4T1 andB16.F10. Effects of radiation and virus infection on surface antigen expression in these tumor lines were assessed. Mechanisms of action of AdlL12/B7.1 were studied by conducting additional experiments with and without depletion of NK-cells and/or T-cells, and by cytotoxic T-lymphocyte assays, and immunohistochemical evaluation of tumor blood vessels. Both B7.1 and IL12 were effectively expressed in both irradiated and unirradiated 4T1 and B16.F10 tumor cells but did not add significantly to radiation-induced cell killing in vitro. However, local tumor infection by AdIL12/B7.1 after irradiation significantly increases the effectiveness of radiotherapy when applied after completion of radiotherapy. The mechanism appears to be complicated, involving a host of factors that included the ability of IL12 to activate T-cells and NK-cells and to inhibit angiogenesis and the ability of radiationto induce apoptosis or necrosis among tumor cells. These data support the combination of radiotherapy with adenovirus-mediated immunotherapy and suggest that the concept of adding genetic immunotherapy after radiotherapy in a combined regimen merits further study.

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Documento generato il 01/12/20 alle ore 10:40:06