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开发一种靶向 M 细胞的微粒平台 BSK02™,用于口服免疫卵巢癌抗原精子蛋白 17。

Development of a M cell-targeted microparticulate platform, BSK02™, for oral immunization against the ovarian cancer antigen, sperm protein 17.

机构信息

Kiromic BioPharma, 7707 Fannin St., Suite 140, Houston, Texas, 77054.

The University of Texas MD Anderson Cancer Center, Department of Lymphoma and Myeloma, and Department of Gastroenterology Hepatology and Nutrition, 1515 Holcombe Blvd, Houston, Texas, 77030.

出版信息

J Biomed Mater Res B Appl Biomater. 2019 Jan;107(1):29-36. doi: 10.1002/jbm.b.34092. Epub 2018 Mar 4.

DOI:10.1002/jbm.b.34092
PMID:29504239
Abstract

Although it only accounts for approximately 5% of all female cancer cases, ovarian cancer (OC) ranks as the fifth leading cause of death due to cancer in women. We have evaluated the potential of an orally administered microparticulate vaccine incorporating an immunodominant epitope peptide derived from the cancer/testis antigen sperm protein 17 (SP17) aberrantly expressed in OC, to retard the progression of the disease. The peptide antigen and the immune-stimulatory toll-like receptor 9 ligand CpG oligonucleotide were incorporated into spray dried microparticles composed of enteric and sustained release polymers together with the Aleuria aurantia lectin targeting microfold cells present in the gut-associated lymphoid tissue. These particles were administered via oral route to mice challenged week prior with SP17-expressing ID8 OC cells. Analysis of splenocytes harvested from vaccinated mice revealed strong activation of IFN-γ+/CD8+ lymphocytes in response to re-stimulation with the SP17 antigen. Moreover, vaccinated animals showed significant retardation of ascites/tumor volume in comparison to placebo-treated animals four weeks after the tumor challenge (p = 0.005). Taken together, our results suggest that vaccination against SP17 using orally administered microparticles could potentially be used as an effective consolidation strategy for OC patients with residual tumor or high probability for relapse following first-line treatments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 29-36, 2019.

摘要

虽然卵巢癌(OC)仅占所有女性癌症病例的 5%左右,但它却是女性癌症死亡的第五大主要原因。我们评估了一种口服给药的微粒疫苗的潜力,该疫苗包含源自在 OC 中异常表达的癌症/睾丸抗原精子蛋白 17(SP17)的免疫优势表位肽,以延缓疾病的进展。该肽抗原和免疫刺激性 Toll 样受体 9 配体 CpG 寡核苷酸被掺入由肠溶和持续释放聚合物组成的喷雾干燥微粒中,并与靶向肠道相关淋巴组织中的微褶皱细胞的 Aleuria aurantia 凝集素结合。这些颗粒通过口服途径施用于在 SP17 表达的 ID8 OC 细胞前一周受到挑战的小鼠。从接种疫苗的小鼠中采集的脾细胞分析显示,在用 SP17 抗原再刺激时,IFN-γ+/CD8+淋巴细胞强烈激活。此外,与安慰剂治疗的动物相比,在肿瘤挑战后四周,接种疫苗的动物的腹水/肿瘤体积明显减慢(p=0.005)。总之,我们的研究结果表明,使用口服给予的微粒对 SP17 进行疫苗接种可能可作为 OC 患者在一线治疗后残留肿瘤或高复发可能性的有效巩固策略。 © 2018 Wiley Periodicals, Inc. J 生物材料研究杂志 B:应用生物材料,107B:29-36,2019 年。

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