A person's immune system makes antibodies to attack germs such as bacteria or viruses, but it will not attack neuroblastoma because the tumor is part of our own bodies. An antibody that attaches to neuroblastoma can be made in a laboratory and then given intravenously to a patient. This antibody will circulate in the bloodstream until it finds and attaches to a neuroblastoma cell. And then the patient's own immune system will attack and kill that neuroblastoma cell.

人体免疫系统会产生抗体去攻击细菌或病毒，但抗体不会去攻击神经母细胞瘤（Neuroblastoma，以下简称NB），因为肿瘤是我们身体的一部分。 然而一种可附着于NB细胞的抗体可以在实验室中制造出来然后静脉注射给患者。这种抗体会在血液系统中循环直到它找到并附着在NB细胞上。然后患者自身的免疫系统就会攻击并杀死NB的细胞。

When 3F8 is injected into the bloodstream, it travels through the body until it attaches to the marker GD2 that is present on all neuroblastoma cells. The attachment of 3F8 to a neuroblastoma cell signals the patient's own immune system (e.g. the white blood cells) to treat neuroblastoma cells as foreign. In other words, the 3F8 directs the patient's immune system, which ordinarily acts only to control infections, to attack neuroblastoma cells and kill them. The treatment is effective even when a patient's immune system has been weakened by chemotherapy treatments because chemotherapy does not affect the part of the immune system that responds to 3F8 antibodies. Over time, as the body's immune system becomes stronger, 3F8 treatments may help the body learn to fight tumors on its own.

3F8被注射进血液后，它会在体内循环直到它附着于所有NB细胞都有的GD2标记物上。附着于NB细胞上的3F8会指示患者的免疫系统（比如：白细胞）把NB细胞当作异物攻击。换句话说，3F8引导病人的免疫系统去攻击并杀死NB细胞，尽管免疫系统通常只扮演控制感染的角色。这种疗法甚至在患者的免疫系统已经被化疗削弱的情况下也是有效的，因为化疗不会影响免疫系统中对3F8抗体有反应的部分。假以时日，随着人体免疫系统的增强，3F8疗法会帮助人体学习如何依靠自身去攻击NB。

When 3F8 is injected into the body, we attach a radioactive isotope called 131-iodine (131I) or 124-iodine (124I). A gamma camera or a PET scanner is then used to scan the patient's body, allowing us to see radioactivity (from the radioactive iodine) in areas with neuroblastoma, but not in parts of the body in which neuroblastoma cells are not present.

在3F8被注射进身体时，我们会在其上附加一种放射性同位素——131-碘 (131I)或 124-碘 (124I)。随后我们会用伽马照相机或PET扫描仪去扫描患者身体，这样我们可以在NB存在的区域观察到放射现象（来自放射性碘同位素），没有NB细胞的人体其他部分不会有此放射现象。

Since 1987, over 25,000 infusions of 3F8 have been safely used in more than 500 patients. During this time, we have continued to make improvements to the effectiveness of 3F8 in killing neuroblastoma.

1987年以来，超过25,000次3F8注射被安全应用于500多患者。在此期间，我们还一直持续地提升3F8杀死NB的效果。

We have a number of different 3F8 protocols available at any given time, each of which is the subject of a clinical trial. Patients are recruited for clinical trials every one to three months. Availability of particular protocols will depend in part on when the patient is ready to begin treatment.

我们随时有很多种不同的3F8方案可用，每一种都通过了临床实验。每一到三个月就会有患者被招募来进行临床试验。特定的方案是否可用取决于患者何时准备好开始治疗。

As of early 2008, we are offering four primary protocols:

截止2008年早些时候，我们提供四种主要方案：

For patients who are in near-complete or complete remission after induction therapy, 3F8 treatment is combined with GM-CSF (a protein that enhances the functioning of 3F8). This is a phase II trial that builds on previous trials that have shown promise. See Protocol 03-077 for more details.

对于那些接受综合治疗后完全缓解或接近完全缓解的患者，3F8疗法会与GM-CSF（一种加强3F8功能的蛋白质）联合应用。 这是一种临床二期实验（a phase II trial），之前的实验已经显示了希望。请查看03-077方案获取详情。

For patients who have disease present after induction therapy but no progression, protocol 03-077 and other protocols described below may be appropriate, depending on the particular circumstances of the patient.

对于接受了综合疗法而仍有症状、但病情没有恶化的患者，视患者的具体情况，03-077方案及其他下面描述的方案将可能被采用。

For patients who do not show sufficient improvement after induction therapy or whose neuroblastoma has recurred or progressed, there are three phase I trials that may be appropriate.  The first combines 3F8 with beta glucan, a substance made from yeast that may enhance the immune system, particularly in conjunction with 3F8, and thus make the 3F8 treatment more effective. See Protocol 05-073 for more details.

对于接受综合治疗后症状没有明显改善，或者NB复发、增长的患者， 将可能采用三种临床一期实验（ phase I trials）方案。第一种是3F8加贝塔葡聚糖。贝塔葡聚糖提炼于酵母菌，它可以增强免疫系统——特别是与3F8联合应用时，因此会增强3F8的疗效。请查看05-073方案获取详情。

Another protocol, sometimes referred to as "dose escalated" 3F8, combines 3F8 with GM-CSF. This trial seeks to maximize the efficacy of 3F8 by determining the highest dose of 3F8 that can be given safely to patients.

另一种方案，有时被指是“渐增剂量”的3F8与GM-CSF的组合。这种方案试图在保证患者安全的前提下使用最大剂量的3F8以寻求最大效果。

The third protocol, often referred to as hot antibodies, couples 3F8 and radioactive iodine. This treatment uses 3F8 to seek out and attach to tumor cells and then to deliver radiation directly to kill the cells without damaging normal tissues.

第三种方案，常被称作“热抗体”，会采用双倍的3F8和放射性碘同位素。这种疗法用3F8寻找并附着于肿瘤细胞，然后直接传递放疗物质进去而不损伤正常组织。

We have a number of 3F8 protocols for patients with high-risk neuroblastoma, including patients with bone marrow disease, bone disease, bulky disease (i.e., solid tumors), and relapsed and refractory disease. See the previous Q&A for an overview of the protocols and eligibility. Our clinical trial database also has information about specific protocols, including eligibility. The brief descriptions provided in the Q&A above and in the online clinical trial database are very general. Each patient must be evaluated to determine which protocol would likely be most effective for him or her. When necessary, we can customize a treatment regimen for individual patients, calling on many modalities, including chemotherapy, surgery, and radiation, to optimize the 3F8 treatment.

针对高危NB患者我们有许多种3F8方案， 所谓高危患者指的是那些有骨髓转移、骨转移、巨大实体肿瘤、复发及产生了耐药性的患者。请查看之前的问题解答来回顾治疗方案及各方案的适用对象。我们的临床实验数据库也有特定治疗方案的信息，包括方案的适用对象。以上问题解答中的简短描述及在线临床实验数据库中的信息是非常概括的。每位患者都必须被仔细评估以决定哪种方案最可能对他或她产生疗效。必要时，我们可以根据患者个体情况自定义一套组合治疗方案，包括化疗，手术，放疗等，以优化3F8的疗效。

3F8 is given intravenously through a Broviac, Hickman, MediPort, or peripheral line (all means of injecting substances into the bloodstream) on an outpatient basis. When being treated with 3F8, patients usually need to be in the clinic for about three hours. This includes time for giving medicines to prevent possible side effects, the 30-minute 3F8 treatment, and one to two hours to monitor the patient for side effects. 3F8 treatment is provided in one- or two-week cycles.

3F8在门诊通过Broviac, Hickman, MediPort, or peripheral line (都指的的是注射用的导管)静脉注射给病人。接受3F8处置时，病人通常需要在医院停留约三小时。这时间包括：注射防止可能的副作用的药物，30分钟的3F8，以及1到2小时用于观察病人的副作用。3F8疗法每一或两周为一疗程。

3F8 treatment is provided in what are referred to as rounds or cycles of one- or two-week periods of daily infusions (except weekends), approximately three weeks off in between rounds. The number of rounds of 3F8 treatment will vary depending upon the protocol, but typically patients will receive at least two to four rounds. The primary consideration in determining the length of 3F8 treatment is that we want patients to receive at least 400 mg/m2 of 3F8 before developing human anti-mouse antibodies (HAMA) to the 3F8. See below for more information about HAMA.

3F8疗法每一周或两周为一个疗程，疗程内每天注射（周末除外），每两个疗程间隔大约三周。3F8疗法具体使用几个疗程会根据方案略作调整，但典型患者会接受至少二到四个疗程。3F8疗法疗程长短的主要考量是在产生针对3F8的“人类抗鼠抗体”（HAMA）之前患者需要接受至少400 mg/m2的3F8。请看下边获取HAMA的更多信息。

Pain is the main side effect. All patients have pain. The second most common side effect is rash (hives with itching), which is an allergic reaction. Pain can lead to a fast pulse (rapid heart rate) and sometimes causes high blood pressure for a short period. Less-common side effects include fever, vomiting, and diarrhea. These problems can usually be taken care of in the outpatient clinic, but sometimes a patient needs to be admitted to the hospital for an overnight stay. In the neuroblastoma outpatient clinic at Memorial Sloan-Kettering, we routinely treat 10 to 12 patients a day with 3F8, and manage side effects of the treatment without much difficulty.

疼痛是主要的副作用。所有患者都感到疼痛。第二常见的副作用是疹子（很痒的麻疹），一种过敏反应。疼痛会导致快速脉搏（快速的心率），有时会导致短期高血压。较少见的副作用包括发烧，呕吐，腹泻。这些问题通常在门诊室就可以处理，但有时病人需要住院至少一天。在斯隆凯瑟琳的NB门诊室，每天我们通常会使用3F8处置10到12位患者，并且比较轻松地处理他们的副作用。

3F8 attaches to GD2, which is present on some nerve cells as well as on neuroblastoma cells. When 3F8 attaches to a nerve cell, a message is sent to the brain, and the patient feels pain. The pain usually starts toward the middle or end of the daily 3F8 treatment and lasts a short time (usually from a few minutes up to an hour). Sometimes discomfort or minimal pain continues during the hours after the treatment. Medicines are used to prevent or control the pain (usually morphine or Dilaudid) and the allergic reactions (usually Benadryl or Vistaril). Ativan and Zofran are other medicines that can help. Patients who were treated with 3F8 beginning in 1986 have been followed, and to date, no permanent side effects on their nerves have appeared.

3F8附着于GD2，GD2会出现于NB细胞，同时也会出现在某些正常神经细胞上。当3F8附着于一个神经细胞时，一条信息被送到大脑，于是患者会感到疼痛。疼痛通常开始于每日3F8疗法的中间或末尾并持续一小段时间（通常是几分钟到一小时）。有时不适或微痛会在治疗后持续几小时。 可以使用药物来防止或控制疼痛（通常是吗啡或甘油桂酸酯）和过敏反应（通常是Benadryl或者Vistaril）。其他常用药有Ativan和Zofran。从1986年至今，根据对接受过3F8疗法的患者的随访调查，未发现有永久性的神经系统副作用。

HAMA stands for "human anti-mouse antibodies." HAMA measures how strongly the body's immune system is reacting to 3F8. 3F8, like most monoclonal antibodies, comes from the white blood cells of a mouse. This means that 3F8 looks different from a human antibody, and thus patients will eventually form antibodies (HAMA) against 3F8. Once a patient has developed HAMA, 3F8 treatments no longer effective because the HAMA blocks the 3F8 from getting to neuroblastoma cells. If the patient has received the desired amount of 3F8 (see next question for further information) by the time HAMA has developed, then treatment with 3F8 will be discontinued. However, if the patient has not yet received the desired amount, it is possible that HAMA may recede, and in that case we can resume 3F8 treatments. We conduct a blood test for HAMA usually one to two weeks after each round of 3F8 infusions. Patients with HAMA usually do not have pain or other side effects from 3F8 treatment.

HAMA是“人类抗鼠抗体”的缩写。HAMA决定了人体免疫系统对3F8的反应会有多强。3F8，如同大多数单体克隆抗体一样，来自老鼠的白细胞。这意味着看上去3F8和人体抗体大不相同，因此患者的免疫系统最终会组织抗体（HAMA）来抵挡3F8。一旦患者产生了HAMA，3F8疗法就不再有效，因为HAMA会阻止3F8到达NB细胞。如果到HAMA产生时患者已经接受了预期剂量的3F8（在下一个问题中有进一步的信息） ，那么3F8疗法将会被终止。无论如何，如果患者还没接受足预期剂量的3F8，有可能HAMA会降低，这种情况下我们会恢复3F8治疗。通常我们会在每个3F8疗程后1到2周做一次血检来检查HAMA。有HAMA的患者通常不会有疼痛或其他3F8疗法的副作用。

HAMA is a positive sign in that it may mean the patient is developing an immune response against the neuroblastoma. However, when HAMA develops before the patient has received the usual 400 mg/m2 of 3F8 (two to four cycles), it may interrupt treatment. (As noted above, once HAMA is present, the 3F8 treatment is no longer effective.) Once HAMA has receded, treatment can resume. Most patients who have received chemotherapy only a short time before 3F8 treatment do not produce HAMA because part of their immune system is too suppressed. In these cases, 3F8 treatment will usually continue for up to two years. The aim of our protocols is to give repeated treatments with 3F8 until HAMA is made, because we believe that approach yields the best chances for cure. We continue to study HAMA to get a better understanding of how it may hurt or benefit patients in the long term.

HAMA某种意义上可以说是一个正面的征兆，因为它可能意味着患者正在产生一个针对NB的免疫反应。然而，如果患者在接受够通常的 400 mg/m2  3F8（二到四个疗程）之前就产生了HAMA的话，这将可能中断治疗。（如同上文指出的，一旦HAMA产生，3F8疗法就不再有效。）一旦HAMA降低，治疗可以恢复。大多数在3F8疗法前接受过即便很短时间化疗的患者都不会产生HAMA，因为他们的部分免疫系统被抑制了。在这些情况下，3F8疗法通常会持续最多两年。我们方案的目的是尽量重复3F8疗法，直到HAMA产生，因为我们相信那样会有最好的痊愈机会。我们仍在研究HAMA以获得更清楚的理解，理解它在长时期内会如何令病人受害或受益。

No. An outside company produces it for us under GMP (good manufacturing practice) conditions. Private funding from foundations and philanthropic benefactors has been critical in paying for the production of 3F8 and for carrying out tests to meet the many governmental safety requirements. We do not charge our patients for 3F8. While we have been successful in getting government funding for much of our laboratory science, the government does not support the manufacturing process for 3F8. It is our hope that 3F8 will soon become a licensed drug. 

不是。一间外部的公司在GMP（优质生产工艺？）标准下为我们生产它。来自财团和慈善家的私人基金会按照严格的流程出资生产3F8并执行测试以满足多种政府安全需求。我们不向患者收取3F8的费用。因为我们已经成功获得了政府基金资助用于我们大量的实验室科学需求，所以政府没有支持3F8的生产。我们希望3F8很快会成为一种正规药品。

Yes, as long as they meet the eligibility requirements of the individual treatment protocols.

是的， 只要他们满足治疗方案对应的甄选资格。

There are a number of phase I and phase II studies, as well as state-of-the-art chemotherapy currently being offered at Memorial Sloan-Kettering. Several promising approaches are in the pipeline waiting to be introduced into the clinic. See our clinical trial database for current information.

目前斯隆凯瑟琳有许多一期和二期研究，例如艺术级（state-of-the-art）化疗。其中一些已经接近于临床应用。请查看我们的临床实验数据库 获得当前信息。