Riemann Helge, Takao Joe, Shellman Yiqun G, Hines Wirt A, Edwards Carl K, Franzusoff Alex, Norris David A, Fujita Mayumi
Department of Dermatology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
Exp Dermatol. 2007 Oct;16(10):814-22. doi: 10.1111/j.1600-0625.2007.00599.x.
Malignant melanoma is a potentially deadly form of skin cancer and people at high-risk of developing melanoma will benefit from effective preventive intervention. Yeast can be used as an efficient vehicle of antigen loading and immunostimulation. Saccharomyces cerevisiae is not pathogenic to humans and can be easily engineered to express specific antigens. In this study, we have developed a melanoma vaccine using a yeast-based platform expressing a full-length melanocyte/melanoma protein to investigate its utility as a prophylactic melanoma vaccine in a transplantable mouse melanoma model. Yeast was engineered and expanded in vitro without technical difficulties, administered easily with subcutaneous injection, and did not show adverse effects, indicating its practical applicability and favourable safety profile. Despite the lack of knowledge of dominant epitopes of the protein recognized by mouse MHC-class I, the vaccine protected mice from tumor development and induced efficient immune responses, suggesting that the precise knowledge of epitopic sequences and the matched HLA type is not required when delivering a full-length protein using the yeast platform. In addition, the vaccine stimulated both CD4(+) T cells and CD8(+) T cells simultaneously. This study provides a 'proof of principle' that recombinant yeast can be utilized as an effective prophylactic vaccine to target patients at high-risk for melanoma.
恶性黑色素瘤是一种潜在致命的皮肤癌形式，有患黑色素瘤高风险的人群将从有效的预防性干预中受益。酵母可作为抗原负载和免疫刺激的有效载体。酿酒酵母对人类无致病性，且可轻松进行基因改造以表达特定抗原。在本研究中，我们开发了一种使用基于酵母的平台表达全长黑素细胞/黑色素瘤蛋白的黑色素瘤疫苗，以在可移植小鼠黑色素瘤模型中研究其作为预防性黑色素瘤疫苗的效用。酵母在体外进行基因改造和扩增没有技术困难，通过皮下注射易于给药，且未显示出不良反应，表明其具有实际适用性和良好的安全性。尽管缺乏对小鼠MHC-I类分子识别的该蛋白优势表位的了解，但该疫苗保护小鼠免受肿瘤发展并诱导了有效的免疫反应，这表明在使用酵母平台递送全长蛋白时，不需要精确了解表位序列和匹配的HLA类型。此外，该疫苗同时刺激了CD4(+) T细胞和CD8(+) T细胞。本研究提供了一个“原理证明”，即重组酵母可作为一种有效的预防性疫苗用于针对有黑色素瘤高风险的患者。
