Directed cytokine expression in tumour cells in vivo using recombinant vaccinia virus.

Therapeutic immunology Pub Date : 1994-01-01
B Acres, K Dott, L Stefani, M P Kieny
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Abstract

Athymic (Swiss nude) and euthymic (DBA) tumour-bearing mice were injected intravenously with various vaccinia virus (Copenhagen strain) recombinants. Several days after inoculation, tumour cells were found to be well infected with infective vaccinia particles, while organs such as liver, spleen, brain and bone marrow showed barely detectable levels or no signs at all of virus infection. Injection of tumour bearing mice with recombinant VV harbouring the cDNA for either huIL-2 or muIL-6 resulted in detectable lymphokine in the sera of injected animals. Injection of tumour-bearing nude mice with VV-IL-6, but not with VV-IL-2, resulted in significant reduction in growth rate of the tumour, and in some cases, complete rejection of the tumour. Tumour-bearing euthymic mice responded differently. Intravenous injection of VV-IL-2, but not VV-IL-6 resulted in reduced growth rate of 50% of tumours and complete rejection of 17% of tumours.

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利用重组痘苗病毒在肿瘤细胞中定向表达细胞因子。
将不同的牛痘病毒(哥本哈根株)重组体静脉注射给荷瘤小鼠athymmic (Swiss nude)和euthymic (DBA)。接种几天后,发现肿瘤细胞被传染性牛痘颗粒感染,而肝脏、脾脏、大脑和骨髓等器官几乎检测不到病毒感染的水平或根本没有病毒感染的迹象。将含有huIL-2或muIL-6 cDNA的重组VV注入荷瘤小鼠,可在小鼠血清中检测到淋巴因子。给荷瘤裸鼠注射VV-IL-6,而不注射VV-IL-2,导致肿瘤生长速度显著降低,在某些情况下,肿瘤完全排斥。荷瘤小鼠的反应不同。静脉注射VV-IL-2,而不是VV-IL-6,导致50%的肿瘤生长速率降低,17%的肿瘤完全排斥。
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