全肿瘤细胞疫苗已经进入临床试验，但效果欠佳，需要创新现有的疫苗模式。肿瘤细胞缺少免疫识别的分子模式，细菌则普遍存在病原相关分子模式（PAMPs），因而能有效诱导免疫反应。为此，本项目拟利用我们自主技术将分枝杆菌蛋白（抗原）粘附于肿瘤细胞表面（将这一过程称为细菌化），同时将表达树突状细胞（DCs）趋化因子MIP-3α的重组腺病毒转染这种细菌化肿瘤细胞（称为细菌化MIP-3α肿瘤细胞），期望利用MIP-3α的活性在疫苗注射部位吸引DCs并特异呈递肿瘤抗原来增强这种全细胞疫苗的免疫反应。在体外研究这种细菌化MIP-3α肿瘤细胞的理化特征和功能活性后将其用作全细胞疫苗，在小鼠肿瘤模型中了解抗肿瘤作用效果和可能的副作用，同时利用免疫学、细胞学等现代生物技术了解这种疫苗是否诱导特异的抗肿瘤免疫反应和肿瘤免疫原性死亡，是否改变免疫微环境等分子机理，为这种细菌化肿瘤细胞疫苗的转化应用提供理论依据。

Various whole-tumor cell vaccines have been developed and some of them have been tested in III clinical trials, but their clinic effectives are short of satisfactory for tumor patients. Therefore, it is necessary that more innovative strategies must be found to developed new whole-tumor cell vaccines. Sensing the presence of a pathogen is the first step for the immune system to mount an effective response to eliminate an invading organism and establish protective immunity. The understanding of innate immunity has led to the discovery of pattern recognition receptors being able to recognize pathogen-associated molecular patterns (PAMPs) of all classes of microorganisms. Thus, in this study, we will use our proprietary technology to adhere the whole proteins (antigens) of mycobacteria (BCG, a comment adjuvant in vaccination) on the tumor cell surface (we called this process as “bacterialized” tumor cells) in which tumor cells are artificially cover the PAMPs of mycobacteria on the tumor cell surface to promote immune system to induce recognize the tumor cell antigens. In addition, to amplify the immune response induced by the bacterialized tumor cell vaccine, we will transfect the bacterialized tumor cells with recombinant (a chemokine of DCs) adenovirus (we called it as “bacterialized MIP-3α tumor cell”), in which the bacterialized tumor cells will express and secrete MIP-3α. In this way, bacterialized MIP-3α tumor cells will attract DCs to the vaccine-injected site and promote antigen presentation and enhance the immune response by the attracted DCs. After in vitro investigate the physico-chemical characteristics and functional activity of the bacterialized MIP-3α tumor cells, we will further use the bacterialized MIP-3α tumor cells as whole-tumor cell vaccine to investigate their anti-tumor effects and potential side-effects in mouse tumor models. Lastly, we will study its immune mechanism, especially those that involved to antigenic cell death and micro-environment. Our current study will offer potentially offer a new approach to develop a effective whole-tumor cell vaccine.