Patel Bindi K, Wang Chao, Lorens Braulio, Levine Alan D, Steinmetz Nicole F, Shukla Sourabh
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States.
Department of NanoEngineering, University of California-San Diego, La Jolla, California 92093, United States.
ACS Appl Bio Mater. 2020 Jul 20;3(7):4179-4187. doi: 10.1021/acsabm.0c00259. Epub 2020 Jun 25.
Cancer vaccines are promising adjuvant immunotherapies that can stimulate the immune system to recognize tumor-associated antigens and eliminate the residual or recurring disease. The aberrant and restricted expression of highly immunogenic cancer testis antigen NY-ESO-1 in several malignancies, including triple-negative breast cancer, melanoma, myelomas, and ovarian cancer, makes NY-ESO-1 an attractive antigenic target for cancer vaccines. This study describes a NY-ESO-1 vaccine based on a bio-inspired nanomaterial platform technology, specifically a plant virus nanoparticle. The 30 nm icosahedral plant virus cowpea mosaic virus (CPMV) displaying multiple copies of human HLA-A2 restricted peptide antigen NY-ESO-1 exhibited enhanced uptake and activation of antigen-presenting cells and stimulated a potent CD8 T cell response in transgenic human HLA-A2 expressing mice. CD8 T cells from immunized mice exhibited antigen-specific proliferation and cancer cell cytotoxicity, highlighting the potential application of a CPMV-NY-ESO-1 vaccine against NY-ESO-1 malignancies.
癌症疫苗是很有前景的辅助免疫疗法，能够刺激免疫系统识别肿瘤相关抗原，并消除残留或复发性疾病。高免疫原性的癌胚抗原NY-ESO-1在包括三阴性乳腺癌、黑色素瘤、骨髓瘤和卵巢癌在内的多种恶性肿瘤中存在异常且受限的表达，这使得NY-ESO-1成为癌症疫苗颇具吸引力的抗原靶点。本研究描述了一种基于仿生纳米材料平台技术，特别是植物病毒纳米颗粒的NY-ESO-1疫苗。展示多个拷贝的人HLA-A2限制性肽抗原NY-ESO-1的30纳米二十面体植物病毒豇豆花叶病毒（CPMV），在表达转基因人HLA-A2的小鼠中表现出增强的抗原呈递细胞摄取和激活，并刺激了强烈的CD8 T细胞反应。来自免疫小鼠的CD8 T细胞表现出抗原特异性增殖和癌细胞细胞毒性，突出了CPMV-NY-ESO-1疫苗针对NY-ESO-1恶性肿瘤的潜在应用。
