Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Nat Med. 2011 Jun 19;17(7):854-9. doi: 10.1038/nm.2390.
Effective cancer immunotherapy requires the release of a broad spectrum of tumor antigens in the context of potent immune activation. We show here that a cDNA library of normal tissue, expressed from a highly immunogenic viral platform, cures established tumors of the same histological type from which the cDNA library was derived. Immune escape occurred with suboptimal vaccination, but tumor cells that escaped the immune pressure were readily treated by second-line virus-based immunotherapy. This approach has several major advantages. Use of the cDNA library leads to presentation of a broad repertoire of (undefined) tumor-associated antigens, which reduces emergence of treatment-resistant variants and also permits rational, combined-modality approaches in the clinic. Finally, the viral vectors can be delivered systemically, without the need for tumor targeting, and are amenable to clinical-grade production. Therefore, virus-expressed cDNA libraries represent a novel paradigm for cancer treatment addressing many of the key issues that have undermined the efficacy of immuno- and virotherapy to date.
有效的癌症免疫疗法需要在有效的免疫激活背景下释放广泛的肿瘤抗原。我们在这里表明，正常组织的 cDNA 文库，从高度免疫原性的病毒平台表达，可以治愈与 cDNA 文库来源相同的组织学类型的已建立的肿瘤。在疫苗接种不充分的情况下会发生免疫逃逸，但逃避免疫压力的肿瘤细胞很容易通过二线基于病毒的免疫疗法进行治疗。这种方法有几个主要优点。使用 cDNA 文库会导致呈现广泛的（未定义的）肿瘤相关抗原，这减少了治疗耐药变体的出现，并且还允许在临床上进行合理的联合治疗模式。最后，病毒载体可以全身递送，而不需要肿瘤靶向，并且易于临床级生产。因此，病毒表达的 cDNA 文库代表了一种新的癌症治疗范例，解决了迄今为止削弱免疫治疗和病毒治疗疗效的许多关键问题。
