back in 1999, two researchers at the national cancer institute (nci) received a long-awaited green light to launch separate studies on cancer care. six months apart, dr. douglas schwartzentruber and dr. larry kwak began enrolling subjects to test an entirely novel weapon in the war on cancer one they hoped would bypass the toxic effects of chemotherapy and give patients a new edge in halting the spread of tumors.
both had the blessings of dr. richard klausner, then nci director. but even klausner, a well-respected researcher, had to be persuaded at first. "i came to the nci being quite skeptical about it," he says of the new strategy.
and he wasn't the only one. what schwartzentruber and kwak were hoping to do was prove they could vaccinate a patient against cancer educate a body to, in essence, recognize and round up tumor cells the same way it polices viruses and bacteria. it certainly made good biological sense: the immune system is the body's built-in defense mechanism, after all, so why not turn it against one of the most ornery diseases around?
the problem, of course, is that a tumor is not exactly a pathogen. what it is, at its core, is a collection of aggressively growing cells that can't stop dividing. it is not entirely foreign, as a virus is; it does not infect healthy cells, as bacteria and viruses do. turning the immune system against cancer cells would involve turning the body's defense mechanisms against a part of itself. designing a vaccine to do this entails creating the biological version of a stealth weapon encased in a smart bomb equipped with a guided missile.
and that was proving to be a bit too challenging. nothing that hundreds of researchers in hundreds of trials had attempted had worked. while the vaccine idea made logical sense, the immune system, it seemed, just wasn't designed to battle cancer this way.
but in june, after nearly a decade of carefully inoculating patients suffering from either advanced melanoma or a type of lymphoma, both schwartzentruber and kwak announced positive outcomes of their trials, at the american society of clinical oncology meeting in orlando, fla. their results, along with those of a trial vaccine against prostate cancer and an early candidate against a type of brain cancer, suggest that we might finally be on the way to unleashing the immune system against the disease.
it's about time. senator edward kennedy's death after a yearlong battle with brain cancer is only the most prominent reminder that while many current treatments are certainly effective, they can be made even better. though malignancies are now being caught earlier than ever before and treatments that target and control the disease are more effective than ever before, cancer is still the second biggest killer in the u.s., claiming more than half a million lives each year. surgery, chemotherapy and radiation can do only so much when tumor cells hide in plain sight and even a single overlooked cell can seed new disease.
that's where a vaccine-based strategy could make a difference. an immune system trained to recognize the first signs of new or recurrent growth can begin to attack malignancies far earlier than the best scans can detect them. and the latest vaccines incorporate clever new insights into how malignant cells can be tagged, exposed and destroyed. "understanding how the immune system works is going to play a significant role in our treatment of cancer going forward," says dr. len lichtenfeld of the american cancer society.
it's not just the biology that is getting better. researchers are even fine-tuning when to give a cancer vaccine. the latest data from the lymphoma trial, for example, suggest that in some cases, the best time to train the immune system might be during a remission, when the body's defensive cells are at their strongest. "it's been a slow evolution, but we are seeing the first inklings that cancer vaccines can work," says dr. steven rosenberg, chief of the surgery branch at nci and a cancer-vaccine pioneer who trained schwartzentruber and kwak.
when is a vaccine not a vaccine?
there may be no better example of what is meant by preventive medicine than the strategy of vaccination. a healthy person is given a tiny taste of a virus flu or polio, say that's too weak to cause illness but just enough to introduce the body to the pathogen. if the virus later shows up for real, the immune system is primed and waiting for it.
that's close to how a cancer vaccine works, but not precisely. most experts see cancer vaccines as a hybrid of treatment and prevention. while it's true that the food and drug administration has approved vaccines against cervical and liver cancer, both are actually designed to fight the viruses most responsible for causing the disease, as opposed to targeting cancer itself human papillomavirus in the case of cervical cancer and hepatitis b in the case of liver tumors.
using vaccines to prevent nonviral cancers in someone who is disease-free is a whole different matter. for one thing, it's much more difficult to determine a person's chance of developing a particular type of cancer than it is to determine the likelihood of being exposed to, say, the influenza virus or chicken pox. what passes for "exposure" in the case of nonviral cancers is a combination of genes and environment and a range of other x factors that can vary from person to person. how do you vaccinate against your family legacy of breast cancer or your constant exposure to secondhand cigarette smoke?
but that doesn't mean the immune system can't be exploited in a different way. cancer vaccines would ideally be used in patients whose disease has already been diagnosed and treated with surgery, chemotherapy or radiation. they would then be immunized as a way to prevent the cancer from coming back and spreading. such metastases are actually the leading cause of death from cancer. "the charm of working with the immune system is that we can use the body's own defense mechanisms to possibly get to that last cancer cell or at least create a surveillance system that keeps that cancer under control," says lichtenfeld.
trial by failure
before they can seek out these smaller, hidden deposits of tumors, however, cancer vaccines must prove that they can actually target and shrink a cancer's more conspicuous growths. this, it turns out, is obvious in theory but devilishly challenging to show in reality.
take melanoma. in 2002 scientists at the john wayne cancer institute in santa monica, calif., thought they had finally figured out a way to turn the immune system against the skin cancer. instead of trying to activate immune cells with snippets of tumor proteins they had created in the lab, they decided to grind up melanoma tumors and use the malignant slurry to prod the right immune cells into action. the result was canvaxin, a vaccine against aggressive melanoma that was loaded up with 20 different tumor-specific components of melanoma, teaching the body new ways to recognize the disease. more than 1,500 patients were given the vaccine after being treated with surgery and chemotherapy. in the first five years of follow-up, the shot proved safe and worthy of moving into the most advanced level of human testing. but in april 2005, the scientists and the biotech company they had enlisted to develop the vaccine were forced to stop their studies when it became obvious that the vaccinated patients were not living any longer than the unvaccinated ones. "that put a damper on things," says schwartzentruber. "they had what they thought was a promising start, and it was an international, multi-institutional study with a large number of patients."
in retrospect, schwartzentruber says, the problem may have been that the vaccine was forced to work alone. even the most well-sensitized immune system may be fooled by the homegrown nature of cancer, recognizing malignant cells as just another part of the body which they are and thus giving them a pass. when the cancer finally grows big enough to represent a real threat, it's too late.
schwartzentruber thinks he has a way around that problem. in some trials, after giving his vaccine to patients with advanced melanoma that has spread to other tissues, he adds an immune stimulator called interleukin-2 (il2) for reinforcement. alone, the vaccine would not cause any tumors to shrink. the il2 treatment itself wasn't very effective either; it shrank tumors in only 10% of patients. but combining the vaccine and il2 has caused tumors in 22% of patients to regress a doubling of effectiveness. "this teaches us a lesson: that combinations of biologic treatments are more powerful than their individual components," says schwartzentruber.
kwak and his collaborators, led by dr. stephen schuster at the university of pennsylvania, see a similar power in pairing. their vaccine, against a form of non-hodgkin's lymphoma known as follicular lymphoma, takes a slightly different, more personalized approach. rather than relying on a commonly found antigen or snippet of cancer protein to teach the body to recognize the malignancy, they designed each vaccine using individual patients' specific lymphoma profiles. they then partnered this customized concoction with another immune stimulator, gmcsf. patients receiving the combination remained in remission on average 44 months after the vaccination, a 47% improvement in disease-free survival compared with those getting the uncustomized vaccine, who stayed in remission for just 30 months.
this study is also the one that yielded the most evidence that the best time to inoculate patients is when they're in remission from their disease. while schwartzentruber elected to administer his melanoma vaccine when his subjects were in the most advanced stages of illness, kwak and his colleagues decided to capture the immune system at its best. they waited until the patients had been in remission for six months after chemotherapy, which rid the body of the bulk of the tumor burden. give the immune system a break from that life-or-death battle, and it might be better able to do the surveillance work of corralling stray cells that escape the initial treatment. "i envision that vaccine approaches like this could be useful as maintenance therapy," says kwak. "we would use chemotherapy and surgery to debulk the tumor and then vaccinate to maintain remission."
the riddle of success
another way to make a vaccine more effective might be to manipulate the very nature of the tumor, so that it is a more obvious target for the immune system a little like tying a more colorful fly on a fishing hook. the idea, says dr. patrick hwu, chair of melanoma oncology at the university of texas' m.d. anderson cancer center and a member of schwartzentruber's team, is to "get the tumor itself to look like a virally infected site, to get the whole immune system going."
the untreated immune system is not helpless in all of this. rosenberg has biopsied tumors and extracted immune cells called lymphocytes from patients with advanced cancer and has grown these cells in culture. in a test tube, the lymphocytes are perfectly capable of killing tumor cells. but in the body, for some reason, they can't seem to stop a lesion from growing. so for melanoma, some researchers are working with a cream that can increase a tumor's "foreignness" to the immune system, tagging it to look more like an unwelcome virus and less like a familiar self cell. other groups are testing ways to shut off the immune suppressors that the tumor sends out to hinder the natural seek-and-destroy tendencies of the immune system. that makes sense. supercharging the immune system while the immune suppressors are still at work is a little like revving a car engine without releasing the emergency brake: in both cases, you're not going anywhere. and yet most early vaccine efforts have involved stepping on the gas alone.
one other way to get the immune system moving might be, in effect, to replace it with an entirely new one, says rosenberg. if a vaccine can marshal the body's defenses to recognize and destroy a tumor, could you rebuild those defenses from the ground up and this time design them so they'll be especially good at fighting cancer cells?
rosenberg's thinking is based on the now familiar strategy of the bone-marrow transplant for leukemia and lymphoma, which are blood- and immune-cell cancers. radiation is used to obliterate a patient's cancer-tainted immune cells; those cells are then replaced by a population of new ones harvested from a healthy donor or grown from some of the patient's healthy cells. rosenberg refines this method for melanoma by first exposing immune-system cells to tumor cells in a dish, thus "training" them to sprout proteins that target cancer cells, and only then infusing them into patients. already he has shown that such a fortified mix can cause tumor regression in up to 70% of melanoma patients.
even that, rosenberg says, can be improved on. he is tipping the odds further in favor of the anticancer cells by genetically modifying the tumor-fighting t cells so that cancer cells aren't simply among the ones they recognize but are the only ones they recognize eliminating the distraction of other infections and allowing the t cells to devote all their energy to the malignancy alone. in june he published results showing that such manipulation can cause regression of tumors in one-third of subjects. "i think the most important progress in using the immune system is not by a vaccine but by using cell-transfer approaches," says rosenberg. "those are looking to be far more effective."
measuring that effectiveness will be another challenge. the melanoma- and lymphoma-vaccine studies both tracked only the extent to which tumors regressed and were not designed to document what most cancer experts not to mention patients see as the gold standard of any new therapy: survival. do patients who are vaccinated live longer than those who are not? how do the vaccine's cancer-controlling powers compare with those of the expanding list of drugs designed to sneak in and halt growing lesions by shutting off their supply of nutrients and oxygen or hampering their growth spurts?
solving those riddles might be the most formidable challenge yet for the vaccine field. some experts are already questioning the need for the lymphoma vaccine when a drug, rituximab, exists to control the disease. kwak points out, however, that in addition to being able to seek out small deposits of tumor cells that even the best-targeted drug therapies might miss, vaccines are generally less toxic. rituximab, for instance, can lead to viral infections and heart problems and may be toxic to the kidneys. if, as some researchers hope, cancer is ever to become more of a chronic disease like diabetes, which can be managed for life, finding treatments that are safe and effective over many years becomes critical. "the risk-benefit ratio begins to swing more against chemotherapy or targeted agents for long-term maintenance," says kwak. "whereas a vaccine, with a favorable safety profile, is ideal for that kind of setting."
if that's true, then this first group of cancer vaccines is well on its way to seeding an entirely new field of immune-based treatments for cancer. "in some way, shape or form, our body repairs cancer cells and 'prevents' cancer," says lichtenfeld. "if it didn't, we would have much more cancer than we actually see. how simple it would be for us to take some markers on a cancer cell's surface and create a vaccine to help the body do what it's supposed to do." it's not simple at all, as it turns out, but it's an idea whose power and potential certainly make it worth the effort.
早在1999年，两位美国国家癌症研究所（nci）的研究人员获得了期待已久的许可，得以分别独立地进行一个癌症治疗研究项目。6个月后，道格拉斯·瓦尔兹特鲁布博士和拉里·夸克博士开始加入了课题研究。研究的内容是测试一种对付癌症的新武器，他们希望这种方法能避免化疗的毒副作用，在阻止患者肿瘤扩散方面发挥新的优势。
他们都得到了当时的美国国家癌症研究所所长理查德·克劳斯纳博士的支持。但在最初，即使是这样一位备受尊敬的研究员，也需要做说服工作。“我到美国国立癌症研究所时对此很怀疑。”他如此评价这个新的战略。
而 他并不是唯一对此持怀疑态度的人。瓦尔兹特鲁布和夸克想要做的是证明能用为病人接种疫苗的方式抗击癌症。实际上，就是教导身体像对待病毒和细菌那样，去识 别和围捕肿瘤细胞。这当然在生物学意义上是行得通的——免疫系统毕竟是身体内在的防御机制，所以，为什么不用它来对付最最坏的疾病呢？
当 然，问题在于肿瘤并不真的是一种病原体。在肿瘤的核心是一群无法停止、一直浸润生长的细胞。它不像病毒那样完全是外来的，也不像细菌病毒那样感染健康 的细胞。所以，使用免疫系统来对付癌细胞，就涉及到用人体防御机制来对抗人体自身一部分这样一个问题了。设计一种疫苗来达到这个效果，就意味着要制造一种 生物上的隐形武器，这种隐形武器被包装在一个带制导的灵巧炸弹中。
而这真是有点困难。上百名研究人员试验了上百次，却没得到什么结果。虽然疫苗的想法合乎逻辑，但看上去好像免疫系统天生就不能这样来与癌症战斗。
但在今年6月，在对晚期黑色素瘤或一种淋巴瘤患者精心免疫接种近十年后，瓦尔兹特鲁布和夸克在美国佛罗里达州奥兰多举行的美国临床肿瘤学会会议上宣布了他们实验的积极成果。他们的实验，以及一个前列腺癌疫苗实验、一个治疗一种脑部恶性肿瘤的早期候选疫苗实验的结果表明，发动免疫系统来抗击癌症，这条路最终可 能是可行的。
这如果来得早些就好了。爱德华·肯尼迪参议员在与脑瘤斗争多年后逝世，这一事件大大提醒着我们：尽管现有的很多治疗的确有 效，我们仍然需要更好的治疗手段。尽管现在比以往能更早地发现恶性肿瘤，针对和控制疾病的治疗也比以往更管用，然而，癌症仍然是美国第二大死亡原因，每年 因之死亡的人数超过五十万。手术、化疗和放疗只能针对藏在易观察部位的肿瘤细胞，然而，哪怕只有一个细胞被忽视，都有可能引起新的疾病。
这就是疫苗战略可以有所作为的地方。训练免疫系统识别肿瘤新发或复发初始信号后，它们便能在最早期开始攻击恶性肿瘤，这个时间远早于最好的扫描技术能侦测到这些肿瘤的时间点。最新的疫苗研究也包括对如何标记、暴露和摧毁肿瘤细胞进行新的深入了解。“了解免疫系统的工作机理将在推动癌症治疗进展的过程中发挥非 常重要的作用。”美国癌症学会的莱恩·利希滕菲尔德博士说。
积极进展不仅仅在生物学方面。研究人员还在精细地调整给予癌症疫苗的时机。例如，淋巴瘤试验的最新数据表明，在某些情况下，训练免疫系统的最好时机可能是在恢复期，这时，身体的防御细胞最强壮。“这进展得很慢，但我们正看到的第一丝线索，表明癌症疫苗可以发挥作用。”史蒂芬·罗森堡博士说，他是美国国家癌症研究所外科研究部主任，癌症疫苗方面的先驱者，他指导了瓦尔兹特鲁布和夸克。
疫苗还是疫苗么？
免疫战略是预防性医疗最好的例子。给健康人一小点病毒，比如流感病毒或者脊髓灰质炎病毒，这些病毒非常脆弱，不至于引发疾病，但对让人体认识到某种病原体却恰好足够了。如果该病毒之后真的来了，免疫系统就已经做好了准备。
这 样的描述已经与癌症疫苗的原理比较接近了，但并不完全准确。大多数专家认为癌症疫苗既是治疗手段，也是预防手段。虽然美国食品和药物管理局已经批准了针对宫颈癌和肝癌的疫苗，但两种疫苗实质上都是针对最可能导致这两种病的病毒设计的，而不是针对癌症本身。比如人乳头瘤病毒会导致宫颈癌，乙肝病毒会导致肝肿瘤。
使用疫苗为没病的人预防和病毒无关的癌症完全是另一回事儿。一方面，确定某人得某种特定癌症的可能性比确定某人是否正暴露在某种病毒，比如暴露在流感病毒或水痘带状疱疹病毒下要难得多。就与病毒无关癌症而言，这种“暴露”包括了因人而异的基因、环境以及许多其他未知因素。乳腺癌的家族遗传，或者长期吸二手烟，对于这些因素，怎样才能进行免疫接种呢？
但是，这并不意味着不能用其他方式来利用免疫系统。癌症疫苗是特别适合用在已经被诊断患病，并已通过手术或放化疗进行治疗的患者身上的。然后，对他们进行免疫接种，来防止癌症复发扩散。要知道，转移其实才是癌症致死的首要原因。“从事免疫系统方面工作的魅力就是可以利用人体自身的防御机制，可能去杀死最后一个癌细胞，或这至少建立一个监测系统去控制癌症。”利希滕费尔德说。
从实验失败中得到启示
在使用用癌症疫苗找出更小更隐蔽的肿瘤前，必须先验证它们确实能针对特定癌症并且使快速生长的癌肿缩小。这一点在理论上显而易见，但事实证明，在现实中这非常具有挑战性。
以 黑色素瘤为例。2002年，加利福尼亚州圣莫尼卡约翰·韦恩癌症研究所的科学家曾认为最终找到了一个让免疫系统对抗皮肤癌的方法。他们决定粉碎黑色素瘤，用这些肿瘤混合液，而不是用实验室制备的肿瘤蛋白质片段来刺激正常免疫细胞发挥作用。使用这种方法，他们制成了治疗浸润性黑色素瘤的疫苗康维辛（canvaxin），这种疫苗中有20种不同的黑色素瘤肿瘤特异性成分，来把新的疾病识别方法教给人体。超过1500名病人在接受手术和化疗后接种了这种疫苗。头5年的随访证明疫苗是安全的，可以进入最后的药物人体实验。但在2005年4月，这些科研人员和中标开发这种疫苗的生物技术公司被迫停止了这项研究，因为可以明显看到，接种疫苗的患者并不比未接种的生存得久。“这是个很大的挫折，”瓦尔兹特鲁布说，“他们本以为开端很不错，要知道，这是一个国际性多机构的研究，有很多病人参与了研究。”
回想起来，瓦尔兹特鲁布说，问题可能是该疫苗只被单独应用。即使是最敏感的免疫系统也可能被癌症体内生成的特点所迷惑，只把恶性肿瘤细胞当成是身体的另一部分——事实确实如此——然后放过了它们。当癌肿最后大到真的构成威胁时，一切都为时已晚了。
瓦尔兹特鲁布认为，解决这个问题，他有一个办法。一些试验中，对一些已扩散的晚期黑色素瘤患者，他在使用疫苗后加了一种叫白细胞介素2的免疫刺激药物，以增强用药效果。如果单独使用，疫苗不会使癌肿缩小。而单独使用白细胞介素2治疗效果也并不十分明显，只有10％的病人肿瘤有所缩小。但是，联合应用疫苗和白细胞介素2，22％的患者肿瘤缩小，也就是说有效率提高了一倍。“这就告诉我们，联合应用生物疗法效果会大大超过单独应用。”瓦尔兹特鲁布说。
美国宾夕法尼亚大学斯蒂芬·舒斯特博士领导的夸克和他的合作者也观察到了类似的现象。他们的疫苗是治疗一种非霍奇金淋巴瘤——滤泡性淋巴瘤的。疫苗采用一种略微不同的更个性化的方式。他们根据每位病人不同淋巴瘤的情况，设计不同的疫苗，而不是用常见抗原或者肿瘤蛋白质片段来告诉人体如何辨别肿瘤。然后，他们将这种根据每位病人情况设计的疫苗与另一种免疫刺激药物gmcsf合用。联合使用了这两种药物的患者在接种后平均缓解期为44个月，这个无病生存期比未接种这种个性化疫苗的患者提高了47%，未接种的患者缓解期平均只有30个月。
这项研究也得到了充分的证据来证实，病人接种的最佳时机是病后缓解期。但是瓦尔兹特鲁布选择在病人疾病最晚期使用黑色素瘤疫苗，而夸克和他的同事们却决定在免疫系统最强的时候把它争取过来。他们在病人化疗缓解后再等待六个月，以减轻患者体内的肿瘤负荷。让免疫系统在生死搏斗后获得一些休息，这也许能让免疫系统更好地把最初治疗漏网的肿瘤细胞一网打尽。“我设想，这样使用疫苗做为一种维持治疗可能更管用，”夸克说，“我们用化疗和手术摧毁大部分肿瘤，然后用免疫方法维持缓解。”
成功之谜
另 一种提升疫苗效果的方法是用疫苗改变肿瘤的性质，让它们能更明显地被免疫系统识别，就像在鱼钩上绑上彩带一样。帕特里克·胡博士是德克萨斯大学m.d. 安德森癌症中心黑色素瘤肿瘤学部的主任，是瓦尔兹特鲁布小组的成员。他说，这个想法是“让肿瘤本身看上去像一个病毒感染灶，于是整个免疫系统会去攻击 它”。
即使免疫系统未经疫苗治疗，它也并非对肿瘤听之任之。罗森伯格对肿瘤做了活检，从晚期癌症病人体内提取出了一种称为淋巴细胞的免疫细胞，并在培养基中培养了这些细胞。在试管中的这些淋巴细胞对肿瘤细胞有很强的杀伤能力。但在体内，出于某些原因，它们似乎无法阻止病变发展。所以，对于黑色素瘤，一些研究人员正在研究一种能让肿瘤变得更易被免疫系统识别为外来物的乳剂来标记肿瘤，让它看上去更像一个不受欢迎的病毒，而不像一个普通的自身细胞。其他研究小组正在尝试阻断肿瘤发出的免疫抑制信号，这些信号会阻碍免疫系统原本的搜索摧毁取向。这种思路有一定道理。如果在免疫抑制仍然在发挥作用的情况下增强人体免疫系统，这有点像一边踩油门一边踩刹车，无论怎么做，都得不到效果。然而，目前很多早期的疫苗都只是相当于光起着踩油门的作用，而没放掉刹车。
另一个让免疫系统起作用的办法实际上可能就是把它换一个新的，罗森伯格说。如果疫苗能重整身体防御系统，让它们识别和摧毁肿瘤，那能不能重新从头再建立一套呢，这次可以把它们设计得特别擅长于抗击肿瘤细胞。
罗 森伯格的想法基于骨髓移植技术。骨髓移植技术目前已经比较成熟，被用于治疗白血病淋巴瘤等血和免疫细胞恶性肿瘤。骨髓移植的方法是，先用放疗除去病人带有 恶性肿瘤的免疫细胞，然后用从健康捐献者获取或者由病人本身健康细胞长成的新的细胞去替代它们。罗森伯格为治疗黑色素瘤优化了这个方法，即先在培养皿中让免疫细胞接触肿瘤细胞，这样就“培训”了这些免疫细胞，让它们萌发出对付癌细胞的蛋白质，再把它们注入患者体内。他已经证明，这种经强化的免疫细胞混合物能让70％的黑色素瘤患者肿瘤归转。
罗森伯格说，这种方法可以继续改进。他正在用遗传改造攻击肿瘤的t细胞的方法，来进一步优选抗癌细胞。这样，癌细胞就不只是免疫细胞可识别的攻击对象之一了，它们成了免疫细胞唯一识别并攻击的对象。所有其它会让免疫细胞分散精力的感染都被排除掉，让t 细胞集中所有力量，只对付肿瘤这一个敌人。他在6月公布的结果显示，这种处理可以让三分之一的患者肿瘤归转。“我想，在各种利用免疫系统的方法中，最重要的进展不是使用疫苗，而是使用细胞转移的方式，”罗森伯格说，“这样做看上去更有效得多。”
如何测量有效性将是另一个挑战。在黑色素瘤和淋巴瘤疫苗的研究中都仅仅跟踪了肿瘤的归转程度，并没有验证大多数肿瘤专家——更不用说病人——评价一种新疗法的金标准：生存率。用了疫苗的病人比没用的活得更久么？大多数抗癌药物切断肿瘤营养或氧供应或者扰乱生长突增，以此潜入并中止病变发展，这类药物的名单正变得越来越长。和这些药物相比，疫苗的抗癌效果又如何？
解开这些谜团可能是当前对疫苗研究领域最艰巨的挑战。一些专家已在质疑，当已经有一种叫美罗华（rituximab）的药能控制淋巴瘤时，是否还要去研究淋巴瘤疫苗。夸克指出，除了能够找出连最好的靶向治疗药物都可能错过的少量肿瘤细胞外，疫苗还有一个优势，就是一般毒性较低。以美罗华为例，就可能导致病毒感染和心脏问题，也可能有肾毒性。如果像一些研究人员希望的那样，癌症最终将成为一种类似糖尿病的慢性病，可以终身控制 的话，那么，去寻找一种使用多年仍然安全有效的治疗方法是至关重要的。“从长期维持的角度看，风险收益的天平会离化疗或者靶向治疗药物更远的，”夸克说， “反之，具有良好安全性的疫苗，从这个角度看更为理想。”
如果确实如此，那么这第一组癌症疫苗就恰恰正播种着癌症免疫治疗的一个全新领域。“从某些方面或形式上说，我们的身体会去修复癌细胞并‘预防’癌症，”利希滕费尔德说，“如果不是这样的话，我们会比目前实际看到的更容易得癌症。从这个意义上说，我们用癌细胞表面的一些标记物去研制疫苗，来帮助身体去做它应做的事，这个道理很简单。”事实证明这并不简单，但这种想法是有效果和潜力的，一定值得为之去努力。