Plant Viral Nanoparticle Conjugated with Anti-PD-1 Peptide for Ovarian Cancer Immunotherapy.
Plant Viral Nanoparticle Conjugated with Anti-PD-1 Peptide for Ovarian Cancer Immunotherapy.
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结合抗pd -1肽的植物病毒纳米颗粒用于卵巢癌免疫治疗。
DOI：
10.3390/ijms22189733
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发表时间：
2021-09-08
影响因子：
5.6
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Gautam A;Beiss V;Wang C;Wang L;Steinmetz NF
免疫疗法在癌症治疗中具有巨大的潜力，特别是当治疗方案结合起来以实现沿癌症免疫周期的途径之间的协同作用时。在之前的工作中，我们证明了原位接种植物病毒豇豆花叶病毒（CPMV）可以激活和招募先天免疫细胞，从而将免疫抑制的肿瘤微环境重新编程为免疫激活状态，从而在肿瘤小鼠模型和犬患者中产生强大的抗肿瘤免疫。CPMV治疗还增加了肿瘤微环境中效应T细胞上的检查点调节因子的表达，如PD-1/PD-L1，我们证明了与免疫检查点治疗的联合进一步改善了治疗结果。在目前的工作中，我们验证了CPMV可以与抗pd -1肽结合以取代昂贵的抗体治疗的假设。具体来说，我们开始测试抗pd -1肽的多价展示（SNTSESF）是否会比CPMV和可溶性肽的组合增强疗效。采用腹腔内卵巢癌的同基因小鼠模型测试了这些方法的有效性。CPMV联合抗pd -1肽（SNTSESF）可提高疗效；然而，只有当SNTSESF与CPMV结合而不是作为游离肽添加时，才能观察到其抗转移性卵巢癌的效力增加。这可以通过纳米颗粒制剂与游离肽在体内命运的差异来解释；较大的纳米颗粒有望表现出较长的肿瘤停留时间和有利的肿瘤内分布。我们的研究为植物病毒原位接种策略提供了新的设计原则。
Immunotherapy holds tremendous potential in cancer therapy, in particular, when treatment regimens are combined to achieve synergy between pathways along the cancer immunity cycle. In previous works, we demonstrated that in situ vaccination with the plant virus cowpea mosaic virus (CPMV) activates and recruits innate immune cells, therefore reprogramming the immunosuppressive tumor microenvironment toward an immune-activated state, leading to potent anti-tumor immunity in tumor mouse models and canine patients. CPMV therapy also increases the expression of checkpoint regulators on effector T cells in the tumor microenvironment, such as PD-1/PD-L1, and we demonstrated that combination with immune checkpoint therapy improves therapeutic outcomes further. In the present work, we tested the hypothesis that CPMV could be combined with anti-PD-1 peptides to replace expensive antibody therapies. Specifically, we set out to test whether a multivalent display of anti-PD-1 peptides (SNTSESF) would enhance efficacy over a combination of CPMV and soluble peptide. Efficacy of the approaches were tested using a syngeneic mouse model of intraperitoneal ovarian cancer. CPMV combination with anti-PD-1 peptides (SNTSESF) resulted in increased efficacy; however, increased potency against metastatic ovarian cancer was only observed when SNTSESF was conjugated to CPMV, and not added as a free peptide. This can be explained by the differences in the in vivo fates of the nanoparticle formulation vs. the free peptide; the larger nanoparticles are expected to exhibit prolonged tumor residence and favorable intratumoral distribution. Our study provides new design principles for plant virus-based in situ vaccination strategies.
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影响因子：
15
作者：
Presolski SI;Hong V;Cho SH;Finn MG
通讯作者：
Finn MG
影响因子：
14
作者：
Mao C;Beiss V;Fields J;Steinmetz NF;Fiering S
通讯作者：
Fiering S
DOI：
10.1038/nrc4019
发表时间：
2015-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Bowtell DD;Böhm S;Ahmed AA;Aspuria PJ;Bast RC Jr;Beral V;Berek JS;Birrer MJ;Blagden S;Bookman MA;Brenton JD;Chiappinelli KB;Martins FC;Coukos G;Drapkin R;Edmondson R;Fotopoulou C;Gabra H;Galon J;Gourley C;Heong V;Huntsman DG;Iwanicki M;Karlan BY;Kaye A;Lengyel E;Levine DA;Lu KH;McNeish IA;Menon U;Narod SA;Nelson BH;Nephew KP;Pharoah P;Powell DJ Jr;Ramos P;Romero IL;Scott CL;Sood AK;Stronach EA;Balkwill FR
通讯作者：
Balkwill FR
影响因子：
17.1
作者：
Shukla S;Wang C;Beiss V;Steinmetz NF
通讯作者：
Steinmetz NF
影响因子：
4.9
作者：
Hoopes, P. Jack;Wagner, Robert J.;Fiering, Steven N.
通讯作者：
Fiering, Steven N.