Antibody Response against Cowpea Mosaic Viral Nanoparticles Improves In Situ Vaccine Efficacy in Ovarian Cancer.
Antibody Response against Cowpea Mosaic Viral Nanoparticles Improves In Situ Vaccine Efficacy in Ovarian Cancer.
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DOI：
10.1021/acsnano.9b07865
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发表时间：
2020-03-24
期刊：
影响因子：
17.1
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Shukla S;Wang C;Beiss V;Steinmetz NF
癌症免疫疗法旨在促进免疫系统识别和消除转化细胞。我们已经在几种同基因肿瘤小鼠模型以及患有转移性黑色素瘤的伴侣犬中确定了植物病毒豇豆花叶病毒（CPMV）作为原位疫苗的免疫治疗功效。瘤内注射CPMV可调节局部肿瘤微环境，缓解免疫抑制，增强抗肿瘤免疫力。然而，驱动这种抗肿瘤免疫的病毒核衣壳本身也是一种有效的免疫原，因此在基于重复给药的治疗期间预计会出现抗 CPMV 抗体形式的免疫反应。此外，作为食物链的一部分，预先存在的植物病毒抗体可能很普遍。这种预先存在的抗 CPMV 免疫力的存在可能会影响原位疫苗的免疫治疗功效，并可能产生转化影响。为了解决这些问题，本研究在同基因小鼠卵巢癌模型中评估了 CPMV 原位疫苗在已有抗体存在的情况下的功效。我们的结果表明，先前接触 CPMV 对 CPMV 原位疫苗的功效没有负面影响。引人注目的是，观察到 CPMV 原位疫苗的功效有所提高。因此，这项研究代表了基于植物病毒的原位疫苗转化开发的一个重要里程碑，并减轻了人们对抗 CPMV 抗体存在的担忧，这些抗体是在治疗过程中产生的，但对免疫治疗效果没有影响。
Cancer immunotherapies are designed to facilitate recognition and elimination of transformed cells by the immune system. We have established the immunotherapeutic efficacy of the plant virus cowpea mosaic virus (CPMV) as an in situ vaccine in several syngeneic tumor mouse models as well as in companion dogs with metastatic melanoma. Intratumoral injection of CPMV modulates the local tumor microenvironment to relieve immunosuppression and potentiate antitumor immunity. The viral nucleocapsid that drives this antitumor immunity, however, also is a potent immunogen itself, and thus immune response in the form of anti-CPMV antibodies is expected during the treatment based on repeat administrations. Moreover, being part of the food chain, pre-existing antibodies to plant viruses may be prevalent. The presence of such pre-existing anti-CPMV immunity could potentially impact immunotherapeutic efficacy of the in situ vaccine and could have translational implications. To address such concerns, this study evaluated the efficacy of CPMV in situ vaccine in the presence of pre-existing antibodies in a syngeneic mouse model of ovarian cancer. Our results indicate that prior exposure to CPMV had no negative impact on the efficacy of CPMV in situ vaccine. Strikingly, an improved efficacy of CPMV in situ vaccine was observed. This study therefore presents an important milestone in the translational development of plant viral-based in situ vaccines and alleviates concerns about the presence of anti-CPMV antibodies, which are developed during the course of treatment but have no impact on immunotherapeutic efficacy.
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