FDA批准一种治疗癌症疫苗产品

　 FDA批准一种治疗性癌症疫苗产品

　2010年4月，在经历了多年挫败之后，美国食品与药品监督管理局（FDA）终于通过了第一款治疗性癌症疫苗产品。这就是由美国华盛顿州西雅图市Dendreon公司生产的Provenge （sipuleucel-T）。该疫苗能够使晚期前列腺癌患者的生命延长好几个月。美国马里兰州贝塞斯达美国癌症研究院（National Cancer Institute）的肿瘤医学专家James Gulley认为，Provenge疫苗的成功让其它几款癌症疫苗看到了希望。

　他指出，FDA在批准Provenge疫苗时需要克服一些管理方面的问题，所以Provenge疫苗无疑是癌症疫苗发展史上的一座里程碑，它为后续的癌症疫苗产品趟开了一条新路。

　在近三年时间里，癌症疫苗的研发工作开展得如火如荼，Gulley认为这部分得益于Provenge疫苗的成功，以及其它几款在晚期临床试验中取得突出表现的癌症疫苗的功劳。大型制药公司们都在启动各自的治疗用疫苗（therapeutic-vaccine）商业项目，小型生物技术公司们也对癌症疫苗研发工作表现出了强烈的兴趣。

　在美国，有数百个癌症疫苗的临床试验项目正在开展，美国马里兰州巴尔的摩约翰霍普金斯大学悉尼金梅尔综合癌症中心（Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University）的肿瘤学家Hyam Levitsky认为，现在，癌症疫苗研究领域的前景要比过去20年间任何时候都要光明得多。Levitsky介绍说，每一个打算进入癌症疫苗研发领域的人都会得到这样的保证——“这一行绝对有前途。”

　Levitsky等人都对癌症疫苗的前景非常乐观，他们坚信癌症疫苗一定会成为常规的治疗手段。他们如此自信不是没有理由的，不光是Provenge疫苗带给他们信心，其它正在进行的癌症疫苗临床试验结果也让给了他们充足的理由。所有这些既有的成绩都预示了癌症疫苗在将来的发展机会。癌症疫苗行业里的工作机会，比如研发、制造和实验等等工作都和传统疫苗行业里的一模一样。但是，癌症疫苗是通过激活或增强患者体内免疫反应的手段来清除肿瘤细胞或者致瘤病原体，以达到治疗癌症的目的，所以研发工作比较困难，目前大部分都还处于实验阶段。癌症疫苗的作用机制非常复杂，所以科研人员们也很难制定出一套标准用于指导癌症疫苗的实验和检验工作。如果在癌症肿瘤研发工作中想要有所建树，就得有坚实的免疫学基础，同时还要了解肿瘤与人体免疫系统之间的相互作用关系。

　转化工作

　癌症疫苗主要可以分为两大类，预防性疫苗（prophylactic vaccine）和治疗性疫苗（therapeutic vaccine）。顾名思义，预防性疫苗主要面对的是健康人群，起到预防癌症发病的作用，而治疗性疫苗面对的是患者，提高患者的免疫力，达到治疗癌症的作用。治疗性疫苗一般都是用肿瘤细胞、致瘤病毒或者肿瘤组织里的某些分子制备的，而预防性疫苗则是针对某种特异性的致瘤病毒研发的。实际上，不论是预防性疫苗还是治疗性疫苗，都是采用同一种通用的方法开发的，比如针对某种广泛存在于肿瘤患者体内的分子进行疫苗开发，但是包括Provenge疫苗在内的很多疫苗却是针对每一个患者而量身定做的。

　制备癌症疫苗要比制备普通的预防传染病的疫苗困难得多，这些困难甚至能够让充满信心的科研人员和临床医生们望而却步。研究人员必须确保他们开发的癌症疫苗能够特异性地针对肿瘤细胞发挥作用，而不会对正常人体细胞造成损伤。传统的预防性疫苗主要作用都是保护健康人群不受感染性疾病的伤害，这些人群的免疫机制都是正常的，但是，治疗性癌症疫苗的使用对象都是因为使用化疗药物之后免疫力比较低下的癌症患者。加上疫苗起效需要时间，所以对于那些只有几个月生命的晚期癌症患者就没有太大的意义了。打造个体化的疫苗更是给科学研发和之后的商业化运作带来了麻烦。制备个体化疫苗通常都需要从患者体内提取肿瘤细胞，或者开发出相应的诊断技术帮助筛选出该疫苗对哪些患者有效。美国北卡罗来纳州达勒姆杜克大学医学中心（Duke University Medical Center）的神经肿瘤学家John Sampson指出，进行大型的临床试验、进行个体化操作、寻找科研经费以及获得FDA的批准，这些都是困难重重的工作。”

　任何一个想要开发癌症疫苗的科研人员都必须非常熟悉肿瘤免疫学，大部分基础科研人员比较了解免疫系统和炎症反应在肿瘤发生、发展过程中的作用，只有少数几家研究所设有专门从事肿瘤免疫研究的博士点，其中包括瑞士的洛桑大学（University of Lausanne in Switzerland）和纽约州立大学（State University of New York）等。绝大多数的肿瘤免疫学家要不就是免疫学专业毕业的，要不就是肿瘤生理学专业毕业的。

　刚刚进入或者想要进入癌症疫苗领域的人应该时刻提醒自己，肿瘤相关药物开发行业充满了风险，一款药物从最初的研发到最后走向临床一般都得经历十几年或者更长的时间。Provenge疫苗花费了20年时间，进行了3次III期临床试验才获得FDA的批准。

　德国图宾根CureVac生物技术公司的首席科学官Karl-Josef Kallen介绍说，绝大多数的大型制药企业都还在观望，他们都不太愿意投入到癌症疫苗的早期研究工作当中。Vincent Tuohy是美国俄亥俄州克立夫兰临床研究所（Cleveland Clinic Lerner Research Institute）的免疫学家，他正在努力为一个预防性疫苗争取科研经费，开始I期临床试验，该疫苗主要用于帮助妇女预防乳腺癌。Tuohy指出，他正在各大制药公司间疲于奔命，这些公司的主营业务是癌症的诊断和治疗，现在正打算进入肿瘤预防领域。Tuohy同时也在寻求政府资金和非赢利性机构的支持。

　葛兰素史克公司（GSK）是一个例外，该公司的免疫治疗部门正在为总部设立在比利时里克森萨特的生物研究中心寻找临床研发经理，打算进行早期和晚期癌症疫苗研发工作。据该公司人力资源部门的高级经理Roya Paganini介绍，他们希望找到具有免疫治疗工作，全科肿瘤学或者某种肿瘤专科方面工作经验的人才。

　主要从事研发工作的小型生物技术公司可能提供的工作机会更多。比如，CureVac公司就正在招聘具有博士学位的研发人员，从事疫苗设计和临床试验等工作。他们还打算将癌症疫苗与现有或即将面世的抗癌药物或疗法相结合。

　临床试验

　大部分针对抗癌药物研发工作开展的临床试验培训课程都非常简单，所以对癌症疫苗的临床试验工作没有太大的帮助。比如，癌症疫苗就没有“最大耐受剂量（maximum tolerated dose）”这个概念，这和传统抗癌药物的情况就完全不同。实际上，癌症疫苗的使用剂量、用药方案以及何时终止治疗等情况都和传统的抗癌药物有很大的差别。

　因此，进行免疫学训练（不论是正规的学校训练还是在职的训练）对于癌症疫苗研发工作取得成功非常必要。参与患者诊疗工作的科研项目负责人员通常都要求拥有医学博士学位，内科或儿科医生执照，同时也有好几年肿瘤科的工作经历。免疫学并不是从属于肿瘤学科中的一个二级学科，所以科研人员们在踏入这个领域之初最好就搞清楚自己是否要从事肿瘤免疫学方向。Levitsky建议，在从事肿瘤工作期间，如果对癌症疫苗产生了兴趣，那么最好找一位经验丰富的前辈当老师，同时最好能够参与一到两项临床试验的设计以及结果分析工作。当Gulley结束了他在美国国立健康研究院的实习生涯的时候，他几乎已经完成了一项临床试验工作，同时在他的脑海中也已经为后续的几个项目做出了规划。和Levitsky一起参加培训的学员们还在学习医学院一年级同学们的免疫学课程的同时，参加了专门的学术研讨会和各种医学联谊会，以便能够随时跟上最新的研究步伐。

　开展临床试验需要经验丰富的临床研究辅助人员，这些人长期与项目负责人合作，帮助加快临床志愿者招募的速度，或者帮助降低临床试验的成本。毕业于杜克大学临床研究健康科学专业，取得硕士学位的Sampson表示，他认为需要找到合适的人才，他们是能够为临床试验指明方向，更好、更高效地完成实验的专业人士。杜克大学还为临床医生、护士以及其他科研人员们提供非学历教育培训。

　制备疫苗

　美国马里兰州弗雷德里克美国癌症研究所生物药品研发部门的主任George Mitra认为，从原理上来说，制备癌症疫苗其实和制备单克隆抗体或者其它生物制品没有什么不同，所以并不一定要求所有参与到癌症疫苗制备、质量控制或质量保证工作的人员需要有肿瘤研究工作的背景。不过，开发个体化的癌症疫苗更像是进行一个专门的研究项目，临床医生们需要从癌症患者身上收集肿瘤细胞，利用这些细胞制备成癌症疫苗。因此，制备这种个体化的疫苗就和制备普通的癌症疫苗不同，需要经验更加丰富的工作人员。比如，在制备Provenge疫苗的过程中有一个步骤是白细胞分离（leukapheresis），就是将患者血液中的抗原呈递细胞分离并纯化出来。然后将这些细胞送往Dendreon公司，公司的技术人员使用他们独有的、只在前列腺癌细胞中才有表达的蛋白对细胞进行培养，制备出疫苗。接着，他们将疫苗交给患者的主治医生。用这种疫苗进行治疗需要分别使用三次，每一次都得重新制备新的疫苗进行治疗。

　Levitsky介绍说，虽然个体化疫苗的优势比较明显，但是如果这种个体化的疫苗商业化之后，那么就需要大量拥有博士和硕士学位，同时还有细胞操作方面的工作经历，熟悉血浆分离置换技术、骨髓移植技术或者移植工程学技术的专业人才，这和传统制药企业的需求完全不同。

　如果癌症疫苗产业能够健康、持续的发展下去，相信会有更多的科研人员对此产生兴趣，科研人员们也会多一个选择。这个领域最吸引人的地方就在于它能够真正帮到“身陷绝境”的癌症患者。Gulley指出，对他来说，癌症疫苗最吸引他的地方就是它真的能够改变癌症患者的命运，帮助他们生存下去，而且几乎没有什么副作用。这也是推动他继续在这条道路上往前走的动力，是推动他不断完善癌症疫苗，给癌症患者带来更多福音的力量之源。

　rapid development of the market economy environment to explore public servants ' duty consumption monetization reform has provided a good foundation. The socialization of rear service work has been launched, and rapid progress in some places and departments, duty consumption monetization of carrier and approach to management has been resolved. Third, in recent years, exploring the monetization of duty consumption has made some progress, have gained some experience and can provide reference to the comprehensive reform of the system of public servants ' duty consumption further. Implementing an "honest canteen", standardize official entertaining management; enhancing the telecommunication expense management; elimination of County travel and countryside subsidies; research "village officials" capitalization management of corporate spending, and so on. Finally, group ...

　　18 session to be held in Beijing from November 9, 2013 to 12th. 35 years ago blew the third plenary session of the reform and opening up in the spring breeze, changed, affect the world; today, 35 years later, in the eyes of the nation and the world expect, again to reform mark China, ushered in the 18 session. XI General Secretary pointed out that China's reform has entered a crucial period and the Sham Shui Po District, must be based on greater political courage and wisdom, lose no time in deepening reform in important fields. Dares to crack a hard nut, dares to question the Rapids, which dares to break the barrier of ideas, and dare to benefit cure barriers. Deepening reform and opening up is on schedule to achieve institutional safeguards of the moderately well-off. Under the "five in one" the General layout of socialist modernization requirements, 18 session of the decision was a "five in one" and the improvement of overall scheme of reform, will promote an integrated and coordinated economic, political, cultural, social and ecological civilization construction of the five reforms and the party's construction in the area of institutional reform.

　The "five in one" programme is to achieve a comprehensive reform of institutional guarantees for objectives of build a well-off society, the smooth progress of the construction of a well-off society and reform the objectives of the programme.

　One, holding time and place importance on November 9, 2013 to the 18 session of the 12th Beijing since 1978, 35, have been 7 plenary session, each time on major issues of political and economic life of the country has made important deployment. In accordance with PRC political practice, often at every session of the CPC Central Committee in a plenary session was held immediately after the party's Congress, on the theme "personnel", discussing election Central's top leaders, such as the election of the Standing Committee of the political Bureau, through the Central Committee members, decisions, such as members of the Central Military Commission.

　The second plenary session, is held in two sessions before the general election, mainly to discuss a new State personnel issues. But by the third

　rapid development of the market economy environment to explore public servants ' duty consumption monetization reform has provided a good foundation. The socialization of rear service work has been launched, and rapid progress in some places and departments, duty consumption monetization of carrier and approach to management has been resolved. Third, in recent years, exploring the monetization of duty consumption has made some progress, have gained some experience and can provide reference to the comprehensive reform of the system of public servants ' duty consumption further. Implementing an "honest canteen", standardize official entertaining management; enhancing the telecommunication expense management; elimination of County travel and countryside subsidies; research "village officials" capitalization management of corporate spending, and so on. Finally, group ...

　　18 session to be held in Beijing from November 9, 2013 to 12th. 35 years ago blew the third plenary session of the reform and opening up in the spring breeze, changed, affect the world; today, 35 years later, in the eyes of the nation and the world expect, again to reform mark China, ushered in the 18 session. XI General Secretary pointed out that China's reform has entered a crucial period and the Sham Shui Po District, must be based on greater political courage and wisdom, lose no time in deepening reform in important fields. Dares to crack a hard nut, dares to question the Rapids, which dares to break the barrier of ideas, and dare to benefit cure barriers. Deepening reform and opening up is on schedule to achieve institutional safeguards of the moderately well-off. Under the "five in one" the General layout of socialist modernization requirements, 18 session of the decision was a "five in one" and the improvement of overall scheme of reform, will promote an integrated and coordinated economic, political, cultural, social and ecological civilization construction of the five reforms and the party's construction in the area of institutional reform.

　The "five in one" programme is to achieve a comprehensive reform of institutional guarantees for objectives of build a well-off society, the smooth progress of the construction of a well-off society and reform the objectives of the programme.

　One, holding time and place importance on November 9, 2013 to the 18 session of the 12th Beijing since 1978, 35, have been 7 plenary session, each time on major issues of political and economic life of the country has made important deployment. In accordance with PRC political practice, often at every session of the CPC Central Committee in a plenary session was held immediately after the party's Congress, on the theme "personnel", discussing election Central's top leaders, such as the election of the Standing Committee of the political Bureau, through the Central Committee members, decisions, such as members of the Central Military Commission.

　The second plenary session, is held in two sessions before the general election, mainly to discuss a new State personnel issues. But by the third

　plenary session, each session of the Central Committee of national institutions and personnel problems have been arranged, you can concentrate on national development and reforms.

　Previous plenary session is often branded with a central leading collective, often by looking at the third plenum of the initiative to found the current central leadership collective governance characteristics.

　From the analysis of the process of economic reform in China, plenary session, 12 session, 14, 16 plenary session have programmatic meaning, respectively, marking the four stages of China's economic reform, and that the start-up phase of reform, reform, construction phase and perfecting the Socialist market economy framework stage of socialist market economy.

　Previous plenary session topics proposed to the third plenary session of "taking class struggle as the key link," shifted to socialist modernization;

　12 session marked the change from rural to urban, established with public ownership as the Foundation of a planned commodity economy;

　13 session at a time when both the old and the new system change, governance and rectify the economic order; 14 ... Fair and efficient and authoritative Socialist judicial system, safeguard the people's interests.

　Legal authority to uphold the Constitution, deepening the reform of administrative law enforcement, ensure that the right to exercise judicial power independently and impartially according to law the prosecution, perfecting the running mechanism of judicial power, improve the system of judicial protection of human rights. Plenary session, Affairs the right to adhere to the system, and let the people authority to let the power run in the Sun, is shut up in a cage of the system power policy. Decision Science, implementation should be constructed strong, supervise the running of powerful system, improve the system of punishing and preventing corruption, promoting political integrity, and strive to achieve cadres ' honest and Government integrity, clean politics.

　To form a scientific and effective coordination of power restriction and mechanisms to strengthen anti-corruption institutional innovation and institutional protection, sound improvement style normal system. Plenary session, building a socialist culture in China, enhancing national cultural soft power, must adhere to the orientation of advanced Socialist culture, adhere to the development of Socialist culture with Chinese characteristics, adhere to the people-centred work-oriented, further deepening reform of culture.

　To improve the cultural management system, establish and improve the modern market system and building modern public cultural service system, improve the level of culture opening. Plenary session, achieving development results more equitable benefit of all people, we must speed up reform of social programs and solve the issues of concern to the people the most direct and real interest, and better meet the needs of the people.

　To deepen education reform, improve institutional mechanisms for the

　plenary session, each session of the Central Committee of national institutions and personnel problems have been arranged, you can concentrate on national development and reforms.

　Previous plenary session is often branded with a central leading collective, often by looking at the third plenum of the initiative to found the current central leadership collective governance characteristics.

　From the analysis of the process of economic reform in China, plenary session, 12 session, 14, 16 plenary session have programmatic meaning, respectively, marking the four stages of China's economic reform, and that the start-up phase of reform, reform, construction phase and perfecting the Socialist market economy framework stage of socialist market economy.

　Previous plenary session topics proposed to the third plenary session of "taking class struggle as the key link," shifted to socialist modernization;

　12 session marked the change from rural to urban, established with public ownership as the Foundation of a planned commodity economy;

　13 session at a time when both the old and the new system change, governance and rectify the economic order; 14 ... Fair and efficient and authoritative Socialist judicial system, safeguard the people's interests.

　Legal authority to uphold the Constitution, deepening the reform of administrative law enforcement, ensure that the right to exercise judicial power independently and impartially according to law the prosecution, perfecting the running mechanism of judicial power, improve the system of judicial protection of human rights. Plenary session, Affairs the right to adhere to the system, and let the people authority to let the power run in the Sun, is shut up in a cage of the system power policy. Decision Science, implementation should be constructed strong, supervise the running of powerful system, improve the system of punishing and preventing corruption, promoting political integrity, and strive to achieve cadres ' honest and Government integrity, clean politics.

　To form a scientific and effective coordination of power restriction and mechanisms to strengthen anti-corruption institutional innovation and institutional protection, sound improvement style normal system. Plenary session, building a socialist culture in China, enhancing national cultural soft power, must adhere to the orientation of advanced Socialist culture, adhere to the development of Socialist culture with Chinese characteristics, adhere to the people-centred work-oriented, further deepening reform of culture.

　To improve the cultural management system, establish and improve the modern market system and building modern public cultural service system, improve the level of culture opening. Plenary session, achieving development results more equitable benefit of all people, we must speed up reform of social programs and solve the issues of concern to the people the most direct and real interest, and better meet the needs of the people.

　To deepen education reform, improve institutional mechanisms for the

　rapid development of the market economy environment to explore public servants ' duty consumption monetization reform has provided a good foundation. The socialization of rear service work has been launched, and rapid progress in some places and departments, duty consumption monetization of carrier and approach to management has been resolved. Third, in recent years, exploring the monetization of duty consumption has made some progress, have gained some experience and can provide reference to the comprehensive reform of the system of public servants ' duty consumption further. Implementing an "honest canteen", standardize official entertaining management; enhancing the telecommunication expense management; elimination of County travel and countryside subsidies; research "village officials" capitalization management of corporate spending, and so on. Finally, group ...

　　18 session to be held in Beijing from November 9, 2013 to 12th. 35 years ago blew the third plenary session of the reform and opening up in the spring breeze, changed, affect the world; today, 35 years later, in the eyes of the nation and the world expect, again to reform mark China, ushered in the 18 session. XI General Secretary pointed out that China's reform has entered a crucial period and the Sham Shui Po District, must be based on greater political courage and wisdom, lose no time in deepening reform in important fields. Dares to crack a hard nut, dares to question the Rapids, which dares to break the barrier of ideas, and dare to benefit cure barriers. Deepening reform and opening up is on schedule to achieve institutional safeguards of the moderately well-off. Under the "five in one" the General layout of socialist modernization requirements, 18 session of the decision was a "five in one" and the improvement of overall scheme of reform, will promote an integrated and coordinated economic, political, cultural, social and ecological civilization construction of the five reforms and the party's construction in the area of institutional reform.

　The "five in one" programme is to achieve a comprehensive reform of institutional guarantees for objectives of build a well-off society, the smooth progress of the construction of a well-off society and reform the objectives of the programme.

　One, holding time and place importance on November 9, 2013 to the 18 session of the 12th Beijing since 1978, 35, have been 7 plenary session, each time on major issues of political and economic life of the country has made important deployment. In accordance with PRC political practice, often at every session of the CPC Central Committee in a plenary session was held immediately after the party's Congress, on the theme "personnel", discussing election Central's top leaders, such as the election of the Standing Committee of the political Bureau, through the Central Committee members, decisions, such as members of the Central Military Commission.

　The second plenary session, is held in two sessions before the general election, mainly to discuss a new State personnel issues. But by the third

　plenary session, each session of the Central Committee of national institutions and personnel problems have been arranged, you can concentrate on national development and reforms.

　Previous plenary session is often branded with a central leading collective, often by looking at the third plenum of the initiative to found the current central leadership collective governance characteristics.

　From the analysis of the process of economic reform in China, plenary session, 12 session, 14, 16 plenary session have programmatic meaning, respectively, marking the four stages of China's economic reform, and that the start-up phase of reform, reform, construction phase and perfecting the Socialist market economy framework stage of socialist market economy.

　Previous plenary session topics proposed to the third plenary session of "taking class struggle as the key link," shifted to socialist modernization;

　12 session marked the change from rural to urban, established with public ownership as the Foundation of a planned commodity economy;

　13 session at a time when both the old and the new system change, governance and rectify the economic order; 14 ... Fair and efficient and authoritative Socialist judicial system, safeguard the people's interests.

　Legal authority to uphold the Constitution, deepening the reform of administrative law enforcement, ensure that the right to exercise judicial power independently and impartially according to law the prosecution, perfecting the running mechanism of judicial power, improve the system of judicial protection of human rights. Plenary session, Affairs the right to adhere to the system, and let the people authority to let the power run in the Sun, is shut up in a cage of the system power policy. Decision Science, implementation should be constructed strong, supervise the running of powerful system, improve the system of punishing and preventing corruption, promoting political integrity, and strive to achieve cadres ' honest and Government integrity, clean politics.

　To form a scientific and effective coordination of power restriction and mechanisms to strengthen anti-corruption institutional innovation and institutional protection, sound improvement style normal system. Plenary session, building a socialist culture in China, enhancing national cultural soft power, must adhere to the orientation of advanced Socialist culture, adhere to the development of Socialist culture with Chinese characteristics, adhere to the people-centred work-oriented, further deepening reform of culture.

　To improve the cultural management system, establish and improve the modern market system and building modern public cultural service system, improve the level of culture opening. Plenary session, achieving development results more equitable benefit of all people, we must speed up reform of social programs and solve the issues of concern to the people the most direct and real interest, and better meet the needs of the people.

　To deepen education reform, improve institutional mechanisms for the