；选择能诱导强烈CD4+/CD8+T反应的载体是设计肿瘤疫苗的关键。现有疫苗大多采用病毒为载体，但效果并不是很理想。遗传减毒子孢子是一种定向敲除疟原虫肝期发育相关基因的子孢子。减毒子孢子能克服机体的免疫耐受，诱导强烈的疟原虫特异性CD4/CD8+T细胞反应。能否选择遗传减毒子孢子作为构建肺癌疫苗的理想载体诱导强烈的肺癌特异性CD4/CD8+T细胞免疫应答？课题组预实验证实，构建的表达MAGE3的遗传减毒子孢子疫苗确实能有效抵御小鼠肺癌株LLC的攻击。鉴此，本项目拟首先在前期研究基础上，一方面观察该疫苗能否诱导MAGE3特异的抗体和CD4/CD8+T 细胞反应，以抑制肺癌细胞的增殖；另一方面利用B、CD4+和CD8+T细胞敲除小鼠探讨其抗肿瘤的效应机制。同时根据TLR2识别减毒子孢子的前期发现探讨其抗肺癌过程中TLR2信号的作用以及对DC和Treg活化的影响，明确遗传减毒子孢子的载体效应机制

Although MAGE3-engineered DC-base and MAGE3-expressing nonreplicating adenoviral vector could induce MAGE3-specific Th1 response, their inhibitory effect on the growth of lung carcinoma need to be largely improved. As a tolerogenic organ, lung is supposed to potentially suppress the immune response induced by vaccines, which might be a main cause resulted in the failure of the current vaccines against lung carcinoma. Genetically attenuated sporozoites, which could successfully induce robust CSP-specific CD4+ and CD8+ T responses, was thought to be able to overcome the tolerogenic mechanisms of lung. Our preliminary data has shown that MAGE3-expressing genetically attenuated sporozoites could effectively resist to the challenge of LLC, but the underlined menchanisms are still unknown. In this project, we would like to investigate whether the MAGE3-expressing genetically attenuated sporozoite could also inhibit the proliferation of the pre-inoculated LLC and the CD4+/CD8+T response was responsible for this effect. As our previous study showed that TLR2 was involved in the recognition of the attenuated sporozoite lysate and essential for the protective immunity induced by the attenuated sporozoite, we would also like to investigate whether TLR2 is also critical for the anti-tumor protective immunity induced by the MAGE3-expressing genetically attenuated sporozoite acting through DC and Treg. This study would help us to understand the mechanism of anti-tumor protective immunity induced by the MAGE3-expressing genetically attenuated sporozoite, and provide us with novel clues to design effective subunited vaccines against lung carcinoma.