合成菌的肿瘤治疗 Cancer therapy with synthetic bacteria

Views:3270       Publish Time: 2019-03-02

现有的癌症治疗方法（如放疗、化疗、手术和靶向药物）对中晚期癌症，特别是复发和转移的癌症的效果都不理想。癌症患者存活期短，治疗痛苦大，医疗费用高昂，亟需开发更有效的治疗方法。微生物疗法是通过改造细菌、病毒等微生物，使之携带多种生物模块从而实现识别、治疗肿瘤的复杂机能。本项目的研究，旨在利用合成生物学技术改造细菌，开发能广谱靶向治疗多种实体肿瘤，并能切实抑制其转移和复发的新型治疗方法。

然而，无论是驯化、筛选的天然菌株，还是通过传统基因工程技术进行简单改造的细菌，都难以解决如何在降低其毒性的同时，提高对肿瘤的靶向、抑制能力这一难题。因此，虽然国外已有数例使用细菌治疗肿瘤的临床试验，也只是证明了细菌疗法的安全性，迄今为止尚未有任何取得理想治疗效果的临床试验，也没有抗癌细菌制剂投放市场的报道。

近年来合成生物学等前沿生命科学的发展，使细菌治疗癌症的实用化变为可能。利用合成生物学方法，能够实现很多传统基因工程无法完成的改造，从而携带更多的信息，实现更复杂的功能。经过改造后的细菌，将携带多种识别机制，能对多种癌细胞进行智能识别和治疗——广谱识别多种癌症；抑制、杀死不同基因型的癌细胞；既能杀死已高度发展的肿瘤中的癌细胞，也能发现并杀灭机体内残存的癌细胞，减少复发和转移。这样改造细菌将与免疫细胞配合共同对抗癌症。相比传统癌症治疗方法，细菌抗癌技术还有安全、使用简便和成本低廉等重大优势

Existing cancer therapies, such as radiotherapy, chemotherapy, surgery, and targeted drugs, are not effective enough for mid- to late-stage cancers, especially recurrent and metastatic cancers. Cancer patients suffer from short survival periods, severe pain due to treatment, and high medical costs. Therefore, the development of more effective cancer therapies is an urgent need. Microbial therapy aims to recognize and treat tumors by equipping microorganisms such as bacteria and viruses with various therapeutic modules. In this project, we use synthetic biology to engineer bacteria to develop novel therapies that can target a broad range of solid tumors and effectively inhibit cancer metastasis and recurrence.

A major challenge for bacterial cancer therapy development, either through domesticating and screening natural strains or modifying bacteria with conventional genetic engineering, is to reduce the toxicity to the human body while in the meantime, improving the specificity and efficiency in tumor inhibition. So far in the world, a number of clinical trials using bacteria to treat tumors have proven the safety of bacterial therapy, but none of them has achieved the desired therapeutic effects, nor has there been any reports of bacteria-based anti-cancer medications being put on the market.

The development of synthetic biology in recent years has turned the possibility of treating cancer with bacteria into a reality. Using synthetic biology techniques, it is possible to engineer bacterial cells to load them with more information and implement more complex functions than conventional genetic engineering is able to. Engineered bacteria will carry multiple recognition mechanisms, allowing intelligent targeting and treatment of a broad spectrum of cancer cells – identifying, suppressing, and killing cancer cells of different genotypes; killing cancer cells in well-developed tumors as well as detecting and wiping out residual cancer cells to prevent recurrence and metastasis. In this way, engineered bacteria will work together with immune cells to fight against cancer. Bacterial cancer therapies also have significant advantages over traditional cancer treatments in terms of safety, ease of use, and low cost.