Cancer Vaccines肿瘤免疫.doc

Cancer Vaccines癌症疫苗Cancer vaccines have been studied for several decades, but advances in this field have beenslower than for other forms of immunotherapy. They are still mostly experimental treatments at this time. 对癌症疫苗的研究进行了几十年，较其它免疫疗法而言，这个领域的进展可就缓慢的多。目前癌症疫苗通常仍在实验阶段 。Most of us know about vaccines given to healthy people for infectious diseases, such as measles and mumps. These vaccines use weakened or killed viruses, bacteria, or other germs to start an immune response in the body. Putting the immune system on alert against these germs prevents people from being infected with them. 我们都熟悉使健康人们不受传染病侵害的疫苗，如麻疹和腮腺炎疫苗。使用被弱化的或是死亡的病毒、细菌或微生物制造的疫苗启动体内的免疫应答。使人体的免疫系统处在警觉的状态来防止被微生物感染。Some cancer vaccines are designed to work the same way. For example, new vaccines against the human papilloma virus (HPV) may help prevent women from getting cervical cancer, and vaccines against hepatitis B virus (HBV) may lower some peoples risk of getting liver cancer. 一些“癌症疫苗”也是仿照这种方式设计的。例如：乳突淋瘤,papilloma 病毒疫苗可以帮助女性预防宫颈癌，乙肝病毒疫苗可以降低患肝癌的风险。But these vaccines dont target cancer cells; they target viruses that can cause these cancers. True cancer vaccines are a little different. Instead of preventing disease, they are meant to get the immune system to attack a disease that already exists. 但是这些疫苗不将癌细胞作为靶子，而是将导致癌症的病毒作为靶子。真正的癌症疫苗对此有些小小的区别。没有起到防病的作用，而是使免疫系统攻击已经存在的疾病。A cancer vaccine contains cancer cells, parts of cells, or pure antigens. The vaccine increases the immune response against cancer cells that are already present in the body. It may be combined with other substances or cells called adjuvants that help boost the immune response even further. 每种癌症疫苗包含癌细胞、或癌细胞的某个部分、或纯粹的抗原。这些疫苗增强了免疫应答来抵抗已经存在于体内的癌细胞。它也可能和其它物质或是细胞结合成为辅助剂，进一步增强免疫应答。Cancer vaccines are thought of as active immunotherapies because they are meant to trigger your own immune system to respond. They are specific because they should only affect the cancer cells. Vaccines dont just boost the immune system in general; they cause the immune system to attack cells with one or more specific antigens. 癌症疫苗被认为是一种积极的免疫疗法，因为它可以激发你自身的免疫系统来工作。他们被称为是特效药，因为他们只杀灭癌细胞。 疫苗不仅全面提高免疫系统，而且还使免疫系统攻击哪些带有1个或多个特殊抗原的细胞（癌细胞）。While cancer vaccines have shown some promise应答 in clinical trials临床试验, none have yet been approved in the United States to treat cancer. Several types of cancer vaccines are now being studied. 在临床试验中尽管癌症疫苗已经显示了一些疗效，但在美国还没有批准疫苗用于癌症治疗。几种癌症疫苗正在被研究中。Tumor cell vaccines 肿瘤细胞疫苗Tumor cell vaccines are made up of 有什么组成cancer cells that have been removed during surgery手术. The cells are treated in the lab, usually with radiation放射物, so they cannot form more tumors. In most cases, doctors also change the cells somehow, often by adding chemicals or new genes遗传因子, to make them more likely to be seen by the immune system. The cells are then injected into the patient. The immune system recognizes antigens on these cells, then seeks out and attacks any other cells with these antigens that are still in the body. 肿瘤细胞疫苗是由在手术中被切除的癌症细胞制成的。这些肿瘤细胞在实验室通常被放射物处理过，使肿瘤细胞不能再进行繁殖。多数情况，医生们也将细胞加入化学物质或是新的遗传因子，使他们更容易被免疫系统识别。这些细胞被注射到患者身体。患者的免疫系统从这些细胞识别出抗原，然后根据这些抗原特征从患者体内找出带有这些特征的细胞并进行攻击。In some cases, doctors give the vaccine along with adjuvants 辅助 that increase the immune response. The general boost they give to the immune system is meant to make the vaccine work better. 在一些情况下，医生们将疫苗加入一些辅助剂来增强免疫反应。这些加到免疫系统的促进手段通常使疫苗更好的工作Some promising 有前途的 newer versions of these vaccines use tumor cells that are fused to dendritic cells, in the hope of further stimulating促进 the immune system. 有希望一代的疫苗使用肿瘤细胞和树突状细胞结合，更有希望促进免疫系统。A possible advantage of tumor cell vaccines over antigen-based vaccines (described in the Antigen Vaccines section) is that not all cancer antigens have been found yet. Using the whole tumor cell may expose使暴露 the immune system to a large number of important cancer antigens, including some that researchers have not yet recognized. This may make them more effective. 基于抗原的肿瘤疫苗（在抗原疫苗章节描述）的发展潜力是所有的癌症抗原没有被全部发现。使用整个肿瘤细胞给免疫系统来扩大重要的癌症抗原，包括一些研究人员至今没被发现的。The 2 basic kinds of tumor cell vaccines are autologous自体同源 and allogeneic.同种异源的2种肿瘤细胞疫苗是自体同源和同种异源的。 Autologous vaccines 自体同源疫苗Autologous (pronounced aw-tah-luh-guss) means coming from the self. An autologous tumor cell vaccine is made from killed tumor cells taken from the same person in whom they will later be used. In other words, cells are taken from you (during surgery), the vaccine is made from them in a lab, and the cells are injected back into you. Autologous cancer cells may be reinjected shortly after surgery, or they may be grown in the lab or frozen and given later. Although autologous tumor cell vaccines are promising, there are some potential drawbacks:潜在的缺点 自体同源的意思是“来自自身”。一种自体同源肿瘤细胞疫苗是用取自患者自身的被杀死的肿瘤细胞制造的。换言之，手术时取自你身上的癌组织，在实验室制成疫苗，然后注射到你身体内。自体同源癌细胞可能在手术后马上注射到你体内，也可能被在实验室被生长或冷冻起来以后使用。尽管自体同源肿瘤细胞疫苗是很有前途，但他们有一些潜在的缺点。 It can be expensive to create a new, unique vaccine for each patient. Cancer cells tend to mutate变异 (change) over time, so an autologous tumor vaccine might become less effective later if the cancer cells in your body change. Depending on the surgery and the size of your tumor(s), you may not have enough usable cells in the removed tumor to make a vaccine, or there may not be enough to re-treat if the cancer starts growing again. 他的制作费用很贵，因为每个患者都有新的、单一的疫苗。 如果你体内的癌细胞变异， 自体同源的肿瘤疫苗可能疗效减小，因为癌细胞总有变异的可能。 取决于手术和肿瘤尺寸，人们可能不能从手术切除物中获得足够多的可用细胞来制作疫苗，或是疫苗不够治疗又开始生长的癌细胞。Because of these problems, researchers are also looking at ways to create tumor cell vaccines that could work in any patient with a particular kind of cancer. 基于这些困难，研究人员开始制作一种肿瘤疫苗，对任何一个患有确定肿瘤的患者都有效。Allogeneic vaccines 同种异源的疫苗。Allogeneic (pronounced al-oh-jen-ay-ick) means coming from another. These vaccines use cells of a particular cancer type that originally came from someone other than you. 同种异源的意思是“来自别人”。这些疫苗使用特定的癌细胞种类是从别人那里提取来的。Allogeneic vaccines are easier to make than autologous vaccines - they are more like off-the-shelf drugs than a vaccine made specifically for one person. The cells for the vaccine are grown in the lab from a stock of cancer cells kept for that purpose. Some allogeneic tumor vaccines use a mixture of cells, originally removed from several patients. The cells are treated and are usually injected along with one or more adjuvant substances to stimulate the immune system. 同种异源疫苗比自体同源疫苗的制作简单的多，他们更像从药品架子取出的药品，而不想每个患者使用他自己特有的疫苗。研究人员专门储存的癌细胞，在实验室培养后来制作疫苗。有些同种异源的肿瘤疫苗使用了混合的细胞-从几个患者取出的细胞组织。这些细胞被处理后通常和一种或多种辅助剂一起给患者注射，来刺激免疫系统。Although the FDA美国食品及药品管理局 has not yet approved any tumor cell vaccines for general use, they are being studied in clinical trials against many types of cancer, including: 尽管美国食品及药品管理局还没有批准肿瘤细胞疫苗在临床大规模使用，但疫苗在治疗癌症临床研究正在进行，包括： melanoma 黑色素瘤 kidney cancer 肾癌 ovarian cancer 卵巢癌 breast cancer 乳腺癌 colorectal cancer 结肠直肠癌 lung cancer 肺癌 prostate cancer 前列腺癌 non-Hodgkin lymphoma 非霍奇金淋巴瘤 leukemia 白血病Antigen vaccines 抗原疫苗Antigen vaccines boost the immune system by using only one antigen (or a few), rather than whole tumor cells that contain many thousands of antigens. The antigens are usually proteins or pieces of proteins called peptides缩氨酸. While antigen vaccines may be specific for a certain type of cancer, they are not made for a unique patient like autologous cell vaccines are. 提高免疫系统的抗原疫苗仅使用一种（或几种）抗原，而不是使用包含几千种抗原完整的肿瘤细胞。这种抗原通常是蛋白质或者是叫缩氨酸的蛋白片断。抗原疫苗可能被用作治疗特定的癌症，他们不像自体同源细胞疫苗每个患者有唯一的疫苗品种。Scientists have learned how to mass-produce many antigens in the lab. They can also change these antigens to make them more easily recognized by the immune system. This new technology means that large amounts of these very specific antigens can now be given to many patients. 科学家已经掌握了如何在实验室里制造大量的抗原的方法。他们能改变这些抗原使免疫系统更容易识别抗原。这些技术意味着大量的特效抗原能够提供给很多患者。Some antigens cause an immune response only in patients with a certain kind of cancer, while others produce immune reactions to more than one kind of cancer. Scientists often combine several antigens in a vaccine to try to get a stronger immune response. 一些抗原在患者特定病种的肿瘤起免疫反应，有些抗原则能在多种癌症病种起免疫反应。科学家经常在疫苗中使用几种抗原来试图达到更强的免疫反应。Antigen vaccines are being studied to be used against these cancers, among others: 人们正在研究用抗原疫苗以下几种癌症： breast cancer 乳腺癌 prostate cancer 前列腺癌 colorectal cancer结肠癌 ovarian cancer 卵巢癌 melanoma 黑色素瘤 kidney cancer 肾癌 pancreatic cancer 胰腺癌 multiple myeloma 多重骨髓瘤Dendritic cell vaccines 树突状细胞疫苗Dendritic cells are special antigen-presenting cells that help the immune system recognize cancer cells. They break down cancer cells into smaller pieces (including antigens), then hold out, or present, these antigens to T cells. This makes it easier for the immune system cells to react to and attack them. Dendritic cells are the most effective antigen-presenting cells known.树突状细胞是特殊的抗原呈递细胞，帮助免疫系统识别癌细胞。他们将癌细胞打碎成更小的块（包括抗原），然后给与“或出现给”细胞抗原。这样对免疫系统细胞来说更容易对癌细胞反应并攻击。树突状细胞是我们知道到的细胞中最好的抗原呈递细胞。Dendritic cell vaccines, like autologous cell vaccines, must be made individually for each patient. The process used to create them is complex and expensive: 和自体同源细胞疫苗一样，树突状细胞疫苗必需为每个患者专门制造。制作这种疫苗的过程是非常复杂和昂贵的。 Doctors remove some dendritic cells (from the blood) and treat them in the lab to make them multiply, creating many more than were withdrawn. 医生从患者的血液中提取树突状细胞，然后在实验室增殖，即繁殖比提取的更多的细胞。 These cells are then taught, in the lab, to recognize cancer antigens. This is done by exposing them to the antigens in a dish, or by genetically modifying them so that they make their own antigens. Some newer studies are even looking at fusing dendritic cells with tumor cells, creating dendritic cells with tumor antigens on their surface. 在实验室里，这些细胞被“教育”成识别癌症抗原。把树突状细胞和抗原暴露在碟子，或通过遗传修改他们使他们具备自有抗原。有些新的研究观察到，树突状细胞和癌症细胞融合在一起，在癌细胞表面产生癌症抗原的树突状细胞。 The dendritic cells are then injected back into the body. 然后树突状细胞被注射回患者体内。The trained dendritic cells are better able to help the immune system recognize and destroy cancer cells that have those antigens on them. 这些被“训练”的树突状细胞能更好的帮助免疫系统识别和摧毁那些带抗原的癌细胞。The dendritic cell vaccine approach has shown promise in tests in lab animals and in early studies in humans. These vaccines are only available through clinical trials at this time. They are being studied for use in people with these and other cancers: 实验室动物和早期的人体的测试中，树突状细胞疫苗近乎呈现出成功的征兆。目前，这些疫苗只用于临床实验。他们被用于治疗如下癌症的患者： prostate cancer 前列腺癌 melanoma 黑色素瘤 kidney cancer 肾癌 colorectal cancer 直肠结肠癌 lung cancer 肺癌 breast cancer 乳腺癌 leukemia 白血病 non-Hodgkin lymphoma 非霍奇金淋巴瘤Anti-idiotype vaccines 反个体基因型疫苗Every B cell or plasma cell makes only one kind of antibody. The unique part of each type of antibody is called an idiotype.每一种细胞或淋巴细胞只产生一种抗体。这种抗体的唯一的角色被称作为个体基因型。 Antibodies are made when the immune system responds to antigens. But the immune system also makes some antibodies that treat other antibodies like antigens. In other words, sometimes the body makes antibodies against other antibodies. Scientists believe these antibodies against antibodies are important in helping to keep the immune system in check.当免疫系统对抗原产生反应时，抗体产生了。 但是免疫系统也产生一些抗体，Antibodies and antigens fit together like a lock and key. So an antibody to a particular idiotype of another antibody (an anti-idiotype) will usually look like the antigen that triggered cells to make the antibody in the first place (like using the lock itself to make an extra key). Because the anti-idiotype antibodies look like the antigen, injecting them into the body causes the immune system to attack the anti-idiotypes, along with the antigens themselves. Scientists have learned how to make these anti-idiotype antibodies in the lab. They can be used as part of a cancer vaccine because they look like the antigens on the cancer cells in the patients body. Therefore, they can trigger an immune response against that specific cancer. Researchers consider lymphomas to be the most promising targets for anti-idiotype vaccines. This is because all lymphoma cells have unique antigen receptors not present on normal lymphocytes or other normal cells of the body. These unique antigens can be used to make lymphoma vaccines. Early studies of B-cell lymphoma vaccines have been promising. DNA vaccines When tumor cells or antigens are injected into the body as a vaccine, they may cause the desired immune response at first, but they may become less effective over time. This is because the immune system recognizes them as foreign and quickly destroys them. Without any further stimulation, the immune system often returns to its normal (pre-vaccine) state of activity. To get around this, scientists have looked for a way to provide a steady supply of antigens to keep the immune response going. DNA is the substance in cells that contains the genetic code for the proteins that cells make. Cells can be injected with bits of DNA that code for protein antigens. This DNA might be taken up by cells and instruct them to keep making more antigens. These types of therapies are called DNA vaccines. Scientists may be able to do this by removing some of your cells, treating them with DNA that codes for a particular antigen, and then returning them to you. The altered cells would then make the antigen on an ongoing basis to keep the immune response strong. DNA vaccines are now being studied in clinical trials for use against the following cancers, among others: melanoma leukemia prostate cancer head and neck cancer Not all cancer treatments using DNA focus on the immune system. For example, other types of experimental therapy use DNA to treat cancer cells directly by replacing the damaged genes responsible for the cells abnormal growth, or by adding new genes that make the cancer cells more sensitive to anti-cancer drugs. For more information, please see the separate American Cancer Society document, Gene Therapy. Vector-based vaccines These vaccines use special delivery systems (called vectors) to make them more effective. They arent really a separate category of vaccine; for example, there are vector-based antigen vaccines and vector-based DNA vaccines. Vectors are special viruses, bacteria, yeast cells, or other structures that can be used to get antigens or DNA into the body. The vectors are often germs that have been altered to make sure they can no longer cause disease. Vectors may be helpful in making vaccines for a number of reasons. First, they may be used to deliver more than one cancer antigen at a time, which may make the bodys immune system more likely to mount a response. Second, vectors such as viruses and bacteria may trigger their own immune responses from the body, which may help make the overall immune response even stronger. Finally, these vaccines may be easier and less expensive to make than some other vaccines. Many clinical trials of vector-based vaccines are now under way. Cancer Vaccines Show Continuing ImprovementArticle date:2001/05/16 New refinements in cancer vaccines are generating excitement about a new class of targeted therapies ?treatments designed to attack only cancer cells, leaving normal cells largely unfazed ?at this weeks annual meeting of the American Society of Clinical Oncology (ASCO), say experts.Targeted therapies are the future of cancer treatment, says Michael Gordon, MD, associate professor of medicine at the University of Arizona College of Medicine, and moderator of a group of presentations on new therapies at the ASCO conference.Dendritic Cell Vaccine Helps Colon Cancer PatientsTo create a vaccine against colorectal cancer, Lawrence Fong, MD of Stanford University, and colleagues, used an abnormal protein called CEA, which is overexpressed by lung and colorectal cancer cells. In cancer patients, the immune system has trouble recognizing CEA as abnormal, and does not attack it vigorously.In the lab, Fongs team designed an altered CEA protein ?one abnormal enough to spark an immune attack, but so similar to CEA that any immune system cells sent to attack it might also attack CEA, in the process destroying cancer cells carrying CEA on their surfaces. The researchers first gave the patients a growth factor to increase their own production of dendritic cells ?the immune cells that recognize abnormal proteins and signal other, killer immune cells to attack. They harvested the dendritic cells and combined them with the altered CEA protein. The mixture was used to vaccinate 12 patients with advanced colorectal or lung cancer for whom other therapies werent working. All tumors shrank in two patients, with one remaining cancer-free for almost one year; the second patients cancer recurred after 10 months. Cancer stopped growing for six months in two others, but then began to grow again. None of the patients experienced significant side effects.Most of these patients had very advanced disease, so these were good results, notes Fong. Our hope is to make these vaccines more potent, and to try them in earlier-stage disease, possibly even use them to prevent disease, he adds.Lung Cancer Vaccine Helps Some Patients In another cancer vaccine trial, John Nemunaitis, MD, of the University of Pennsylvania, and colleagues vaccinated patients using their own tumor cells, genetically altered to produce a substance called GM-CSF that stimulates the immune system to attack abnormal proteins such as those on cancer cells. Of 22 patients with advanced non-small cell lung cancer (NSCLC) so far vaccinated, all signs of cancer have disappeared in three. Another patients tumors shrank by half. In two other patients, some tumors disappeared while others did not. Tumors stayed the same size in four patients, and tumors in 12 others continued to grow. Also vaccinated were eight patients with early stage NSCLC whose tumors had been surgic