Jourdier T-M, Moste C, Bonnet M-C, Delisle F, Tafani J-P, Devauchelle P, Tartaglia J, Moingeon P
Département Recherche et Développement, Aventis Pasteur, Campus Merieux, 1541 Avenue Marcel Merieux, Marcy l'Etoile, France.
Gene Ther. 2003 Dec;10(26):2126-32. doi: 10.1038/sj.gt.3302124.
We tested the canarypox virus vector ALVAC and the genetically attenuated vaccinia virus vector NYVAC as vehicles for achieving local immunomodulation in domestic animals bearing spontaneous tumours. Following intratumoral administration of ALVAC-, or NYVAC-luciferase in dogs with melanoma, it was demonstrated that viral recombinants remained localized along the needle track, with no virus detectable in the periphery of the tumour. Given these distribution characteristics and their well-documented safety profile, ALVAC- or NYVAC-based recombinants expressing feline or human IL2, respectively, were administered to domestic cats, in order to prevent the recurrence of spontaneous fibrosarcomas. In the absence of immunotherapy, tumour recurrence was observed in 61% of animals within a 12-month follow-up period after treatment with surgery and iridium-based radiotherapy. In contrast, only 39 and 28% of cats receiving either NYVAC-human IL2 or ALVAC-feline IL2, respectively, exhibited tumour recurrences. Based on such results, and in the context of ongoing clinical studies conducted in humans, we discuss the utilization of ALVAC- or NYVAC-based recombinants as viable therapeutic modalities for local immunotherapy or therapeutic vaccination against cancer, both in humans and companion animals.
我们测试了金丝雀痘病毒载体ALVAC和基因减毒痘苗病毒载体NYVAC，作为在患有自发性肿瘤的家畜中实现局部免疫调节的载体。在患有黑色素瘤的犬中瘤内注射ALVAC-或NYVAC-荧光素酶后，结果表明病毒重组体沿针道局部留存，在肿瘤周边未检测到病毒。鉴于这些分布特征及其充分记录的安全性，分别向家猫施用表达猫或人IL2的基于ALVAC或NYVAC的重组体，以预防自发性纤维肉瘤的复发。在未进行免疫治疗的情况下，在接受手术和铱基放疗治疗后的12个月随访期内，61%的动物出现肿瘤复发。相比之下，分别接受NYVAC-人IL2或ALVAC-猫IL2的猫中，只有39%和28%出现肿瘤复发。基于这些结果，并结合正在进行的人体临床研究，我们讨论了基于ALVAC或NYVAC的重组体作为人类和伴侣动物局部免疫治疗或癌症治疗性疫苗接种的可行治疗方式的应用。
