S100A9-Targeted Cowpea Mosaic Virus as a Prophylactic and Therapeutic Immunotherapy against Metastatic Breast Cancer and Melanoma,Advanced Science

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S100A9-Targeted Cowpea Mosaic Virus as a Prophylactic and Therapeutic Immunotherapy against Metastatic Breast Cancer and Melanoma
Advanced Science ( IF 14.3 ) Pub Date : 2021-09-14 , DOI: 10.1002/advs.202101796
Young Hun Chung ₁ , Jooneon Park ₂ , Hui Cai ₂ , Nicole F Steinmetz _{1,

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Affiliation

Prognosis and treatment of metastatic cancer continues to be one of the most difficult and challenging areas of oncology. Treatment usually consists of chemotherapeutics, which may be ineffective due to drug resistance, adverse effects, and dose-limiting toxicity. Therefore, novel approaches such as immunotherapy have been investigated to improve patient outcomes and minimize side effects. S100A9 is a calcium-binding protein implicated in tumor metastasis, progression, and aggressiveness that modulates the tumor microenvironment into an immunosuppressive state. S100A9 is expressed in and secreted by immune cells in the pre-metastatic niche, as well as, post-tumor development, therefore making it a suitable targeted for prophylaxis and therapy. In previous work, it is demonstrated that cowpea mosaic virus (CPMV) acts as an adjuvant when administered intratumorally. Here, it is demonstrated that systemically administered, S100A9-targeted CPMV homes to the lungs leading to recruitment of innate immune cells. This approach is efficacious both prophylactically and therapeutically against lung metastasis from melanoma and breast cancer. The current research will facilitate and accelerate the development of next-generation targeted immunotherapies administered as prophylaxis, that is, after surgery of a primary breast tumor to prevent outgrowth of metastasis, as well as, therapy to treat established metastatic disease.

中文翻译：

S100A9 靶向豇豆花叶病毒作为针对转移性乳腺癌和黑色素瘤的预防性和治疗性免疫疗法

转移性癌症的预后和治疗仍然是肿瘤学中最困难和最具挑战性的领域之一。治疗通常包括化疗，但由于耐药性、不良反应和剂量限制性毒性，化疗可能无效。因此，人们正在研究免疫疗法等新方法，以改善患者的治疗效果并最大限度地减少副作用。 S100A9 是一种钙结合蛋白，与肿瘤转移、进展和侵袭性有关，可将肿瘤微环境调节至免疫抑制状态。 S100A9 在转移前以及肿瘤发展后的免疫细胞中表达并由其分泌，因此使其成为预防和治疗的合适靶点。在之前的工作中，已证明豇豆花叶病毒（CPMV）在瘤内给药时可充当佐剂。在此，证明了全身施用的、靶向 S100A9 的 CPMV 会回到肺部，导致先天免疫细胞的募集。这种方法对于预防和治疗黑色素瘤和乳腺癌的肺转移均有效。目前的研究将促进和加速开发下一代靶向免疫疗法作为预防，即在原发性乳腺肿瘤手术后预防转移，以及治疗已确定的转移性疾病。

更新日期：2021-11-04

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