When mice with human tumors received doses of anti-CD47, which sets the immune system against tumor cells, the cancers shrank and disappeared. 当患上人类肿瘤的老鼠接受一定剂量的抗CD47时，抗CD47就会使免疫系统抗击肿瘤细胞，使癌症病灶缩小，直至消失。
by Sarah C. P. Williams 胡德良 译
| A single drug can shrink or cure human breast, ovary, colon, bladder, brain, liver, and prostate tumors that have been transplanted into mice, researchers have found. The treatment, an antibody that blocks a "do not eat" signal normally displayed on tumor cells, coaxes the immune system to destroy the cancer cells. | 研究人员发现，一种药物可以缩小或消除移植到老鼠身上的人类肿瘤，包括乳腺瘤、卵巢瘤、结肠瘤、膀胱瘤、脑瘤、肝脏瘤和前列腺瘤等。该疗法使用的是一种抗体，这种抗体可以阻断肿瘤细胞上正常展示出来的“不许吃我”信号，诱使免疫系统摧毁癌细胞。 |
| A decade ago, biologist Irving Weissman of the Stanford University School of Medicine in Palo Alto, California, discovered that leukemia cells produce higher levels of a protein called CD47 than do healthy cells. CD47, he and other scientists found, is also displayed on healthy blood cells; it's a marker that blocks the immune system from destroying them as they circulate. Cancers take advantage of this flag to trick the immune system into ignoring them. In the past few years, Weissman's lab showed that blocking CD47 with an antibody cured some cases of lymphomas and leukemias in mice by stimulating the immune system to recognize the cancer cells as invaders. Now, he and colleagues have shown that the CD47-blocking antibody may have a far wider impact than just blood cancers. | 十年前，加州帕洛阿尔托市斯坦福大学医学院的生物学家欧文·魏斯曼发现：比起健康细胞，白血病细胞可以产生更多被称为CD47的蛋白质。魏斯曼和其他科学家还发现：健康的血细胞中也有CD47；当随着血液循环时，CD47就成为一种标志物，标志着它们可以阻碍免疫系统将癌细胞摧毁。各种癌症利用CD47这面旗来欺骗免疫系统，使免疫系统忽视癌细胞的存在。在过去的几年中，魏斯曼的实验证明：利用一种阻断CD47的抗体，可以刺激免疫系统，使免疫系统将癌细胞当作入侵细胞，这样能够治愈一些淋巴瘤和白血病病例。现在，魏斯曼及同事业已证实，阻断CD47的抗体可能远远不只是对血癌有影响。 |
| "What we've shown is that CD47 isn't just important on leukemias and lymphomas," says Weissman. "It's on every single human primary tumor that we tested." Moreover, Weissman's lab found that cancer cells always had higher levels of CD47 than did healthy cells. How much CD47 a tumor made could predict the survival odds of a patient. | “我们所证实的是：CD47不仅仅对于白血病和淋巴瘤是关键的，”魏斯曼说，“它对于我们测试过的每一种人类主要肿瘤都很关键。”此外，魏斯曼的实验还发现，癌细胞总是比健康细胞拥有更高水平的CD47。一种肿瘤产生CD47的多少可以用来预测一个病人存活的几率有多大。 |
| To determine whether blocking CD47 was beneficial, the scientists exposed tumor cells to macrophages, a type of immune cell, and anti-CD47 molecules in petri dishes. Without the drug, the macrophages ignored the cancerous cells. But when the anti-CD47 was present, the macrophages engulfed and destroyed cancer cells from all tumor types. | 为了确定阻断CD47是否有益，科学家们将肿瘤细胞和巨噬细胞（一种免疫细胞）以及抗CD47 分子一起放在培养皿中。在没有抗CD47分子的情况下，巨噬细胞就会忽视癌细胞的存在；当抗CD47存在的时候，巨噬细胞就会吞噬并摧毁来自各种肿瘤的癌细胞。 |
| Next, the team transplanted human tumors into the feet of mice, where tumors can be easily monitored. When they treated the rodents with anti-CD47, the tumors shrank and did not spread to the rest of the body. In mice given human bladder cancer tumors, for example, 10 of 10 untreated mice had cancer that spread to their lymph nodes. Only one of 10 mice treated with anti-CD47 had a lymph node with signs of cancer. Moreover, the implanted tumor often got smaller after treatment -- colon cancers transplanted into the mice shrank to less than one-third of their original size, on average. And in five mice with breast cancer tumors, anti-CD47 eliminated all signs of the cancer cells, and the animals remained cancer-free 4 months after the treatment stopped. | 接下来，研究小组将人类肿瘤移植到老鼠的脚部，因为这个部位的肿瘤监视起来很方便。当研究人员利用抗CD47来治疗这些老鼠之后，肿瘤出现萎缩，并且没有扩散到身体的其他部位。拿接受人类膀胱肿瘤移植的老鼠来说：十个没有接受治疗的老鼠，癌细胞都扩散到淋巴结；在接受抗CD47治疗的十个老鼠中，只有一个老鼠的淋巴结拥有癌症的迹象。此外，接受治疗之后，移植的肿瘤通常会变小——移植到老鼠身上的结肠癌肿瘤平均萎缩到不到原来大小的三分之一。在五个接受乳腺癌肿瘤移植的老鼠中，经抗CD47治疗之后，消除了所有的癌细胞迹象，而且治疗停止4个月之后，仍然没有罹患癌症。 |
| "We showed that even after the tumor has taken hold, the antibody can either cure the tumor or slow its growth and prevent metastasis," says Weissman. | “我们证实，即使在肿瘤形成之后，这种抗体要么可以治愈肿瘤，要么延缓肿瘤的生长并防止转移，”魏斯曼说。 |
| Although macrophages also attacked blood cells expressing CD47 when mice were given the antibody, the researchers found that the decrease in blood cells was short-lived; the animals turned up production of new blood cells to replace those they lost from the treatment, the team reports online today in the Proceedings of the National Academy of Sciences. | 今天，研究小组在《美国国家科学院院刊》在线版上报道说：老鼠接受抗体治疗之后，尽管巨噬细胞也攻击表达CD47的血细胞，但是研究人员发现血细胞降低的情况是短暂的。事实证明，老鼠可以产生新的血细胞来替代治疗中损失的血细胞。 |
| Cancer researcher Tyler Jacks of the Massachusetts Institute of Technology in Cambridge says that although the new study is promising, more research is needed to see whether the results hold true in humans. "The microenvironment of a real tumor is quite a bit more complicated than the microenvironment of a transplanted tumor," he notes, "and it's possible that a real tumor has additional immune suppressing effects." | 剑桥市麻省理工学院的癌症研究人员泰勒·杰克斯称，尽管这项新研究带来了很大希望，但是仍然需要进行更多的研究，以便确定这些研究结果是否同样适用于人类。“一颗真正肿瘤的微环境比移植肿瘤的微环境要复杂得多，”他指出，“真正肿瘤可能有着另外的免疫抑制效应。” |
| Another important question, Jacks says, is how CD47 antibodies would complement existing treatments. "In what ways might they work together and in what ways might they be antagonistic?" Using anti-CD47 in addition to chemotherapy, for example, could be counterproductive if the stress from chemotherapy causes normal cells to produce more CD47 than usual. | 杰克斯表示，另一个问题是CD47抗体将会如何跟现存的治疗方法形成互补：“在哪些方面可能是相辅相成的？在哪些方面可能是互相对抗的？”例如，如果化疗带来的紧张情绪会引起正常细胞比平时产生更多的CD47，那么除了利用化疗之外再利用抗CD47就可能达不到预期效果了。 |
| Weissman's team has received a $20 million grant from the California Institute for Regenerative Medicine to move the findings from mouse studies to human safety tests. "We have enough data already," says Weissman, "that I can say I'm confident that this will move to phase I human trials." | 魏斯曼的研究小组从加州再生医学研究所得到了2000万美元的资助，准备将研究老鼠的发现应用到人类安全试验中来。“我们已经掌握了足够的资料，”魏斯曼说，“我对展开第一期人体试验很有信心！” |
原著：Sarah C. P. Williams
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