题记：斯坦福大学的研究人员创造了“诱饵受体”分子，可防止小鼠出现弥漫性大 B 细胞淋巴瘤 (DLBCL-- diffuse large B cell lymphoma) 和多发性骨髓瘤 (MM)。多发性骨髓瘤MM 和弥漫性大B细胞淋巴瘤 DLBCL 都是由产生抗体的身体 B 细胞产生的癌症。罹患其中的一种，只有不到60%的患者能存活5年。这是两种可怕的血癌，因为可怕，治疗必然艰难；但借助于分子医学还是有望控制其发展和扩散的。

Stanford-Developed “Decoy Molecules” Can Halt the Spread of Cancer

斯坦福大学开发的“诱饵分子”可以阻止癌症的传播

Multiple myeloma is a kind of cancer that develops in a type of white blood cell known as a plasma cell.

多发性骨髓瘤是一种在称为浆细胞的白细胞中发展的癌症。

（注：浆细胞--浆细胞是免疫细胞的一种，人体内的免疫细胞主要是指白细胞尤其是淋巴细胞，淋巴细胞又分为两大类，即T淋巴细胞（thymus dependent lymphocyte  胸腺依赖性[淋巴]细胞）和B淋巴细胞（囊依赖性淋巴细胞(bursa dependent lymphocyte)）。当细菌、真菌、支原体等微生物通过破损的伤口侵入人体时，人体血液中的免疫细胞会很快识别这些入侵者，同时激活细胞的免疫功能，采用各种方式清除这些侵略者，防止机体被感染，其中B淋巴细胞激活后变成浆细胞，分泌相应的抗体，通过抗体包裹、吞噬等方式清除致病的病原微生物。由此可见，浆细胞是活化状态的B淋巴细胞，主要功能是参与清除入侵人体病原微生物的体液免疫反应。血液中的白细胞共有五种，即中性粒细胞Neutrophil、嗜酸性粒细胞eosinophil、嗜碱性粒细胞basophil、淋巴细胞lymphocyte和单核细胞monocyte。）

Stanford cancer team uses the custom molecule sBCMA-Fc V3 to inhibit the development of diffuse large B cell lymphoma and multiple myeloma in mice.

斯坦福癌症团队使用定制分子 sBCMA-Fc V3 来抑制小鼠弥漫性大 B 细胞淋巴瘤和多发性骨髓瘤的发展。

Researchers at Stanford University have created “decoy receptor” molecules that prevent the development of diffuse large B cell lymphoma (DLBCL) and multiple myeloma (MM) in mice.

斯坦福大学的研究人员创造了“诱饵受体”分子，可防止小鼠出现弥漫性大 B 细胞淋巴瘤 (DLBCL-- diffuse large B cell lymphoma) 和多发性骨髓瘤 (MM)。

The molecules, which were recently described in a study published in the Journal of Experimental Medicine (JEM), were also found to be nontoxic in monkeys, indicating they could be used to treat people with either of these deadly conditions, which are two of the most prevalent blood cancers in the world.

最近在《实验医学杂志》(JEM) 上发表的一项研究中描述了这些分子，也发现它们对猴子无毒，这表明它们可用于治疗患有这些致命疾病中的任何一种的人，这是两种世界上最流行的血癌（B 细胞淋巴瘤 (DLBCL) 和多发性骨髓瘤 (MM)）。

Both MM and DLBCL are cancers that arise from the body’s B cells, which make antibodies. Less than 60% of patients who have one of these conditions will survive five years.

多发性骨髓瘤MM 和弥漫性大B细胞淋巴瘤 DLBCL 都是由产生抗体的身体 B 细胞产生的癌症。罹患其中的一种，只有不到60%的患者能存活5年。

Compared with a control (left), treatment with a soluble BCMA decoy receptor (right) increases the number of dying cancer cells (brown) in a multiple myeloma tumor growing in mice. Credit: 2022 Miao et al. Originally published in the Journal of Experimental Medicine.

与对照组（左）相比，使用可溶性 BCMA 诱饵受体（右）治疗会增加小鼠生长的多发性骨髓瘤肿瘤中垂死癌细胞（棕色）的数量。 图片来源：2022 Miao 等人。 最初发表在《实验医学杂志》上。

In recent years, several patients have seen success using genetically modified CAR T cells to target and destroy cancerous B cells. However, this immunotherapeutic strategy often has serious side effects and is unsuitable for older individuals, one of the most common types of people who have MM and DLBCL.

近年来，一些患者已经成功使用转基因 CAR T（注：CAR-T，全称是Chimeric Antigen Receptor T-Cell Immunotherapy，嵌合抗原受体T细胞免疫疗法。这是一个出现了很多年，但是近几年才被改良使用到临床上的新型细胞疗法。和其它免疫疗法类似，它的基本原理就是利用病人自身的免疫细胞来清除癌细胞，但是不同的是，这是一种细胞疗法，而不是一种药。） 细胞靶向和破坏癌细胞 B 细胞。 然而，这种免疫治疗策略往往有严重的副作用，不适合老年人，老年人是最常见罹患 MM（多发性骨髓瘤） 或 DLBCL（弥散性大B细胞淋巴癌的）。

“Safe and effective targeted therapies are therefore still needed for patients who exhaust currently available treatment options,” says Dr. Yu Rebecca Miao, an instructor in the Department of Radiation Oncology at Stanford University.

斯坦福大学放射肿瘤学系讲师 Yu Rebecca Miao 博士说：“因此，对于用尽当前可用治疗方案的患者，仍然需要安全有效的靶向治疗。”

Miao co-led the new research with Stanford University’s Dr. Kaushik Thakkar and Professor Amato J. Giaccia, who currently works at the University of Oxford’s Oxford Institute for Radiation Oncology. The Medical Research Council UK provided partial funding for the research.

Miao 与斯坦福大学的 Kaushik Thakkar 博士和目前在牛津大学牛津放射肿瘤研究所工作的 Amato J. Giaccia 教授共同领导了这项新研究。 英国医学研究委员会为这项研究提供了部分资金。

Two cell signaling proteins called APRIL and BAFF were hypothesized to be potential therapeutic targets for MM and DLBCL by Miao and colleagues. APRIL and BAFF regulate the growth of healthy B cells by binding to several different cell surface receptor proteins.

Miao 及其同事假设称为 APRIL 和 BAFF 的两种细胞信号蛋白是多发性骨髓瘤（MM ）和 弥散性大B细胞淋巴癌（DLBCL） 的潜在治疗靶点。 APRIL 和 BAFF 通过与几种不同的细胞表面受体蛋白结合来调节健康 B 细胞的生长。

However, increased levels of APRIL and BAFF encourage the development and survival of malignant B cells, promoting the spread of blood cancer and the development of treatment resistance. Particularly, APRIL is connected to the development of MM, while BAFF is connected to DLBCL.

然而，增加的 APRIL 和 BAFF 水平会促进恶性 B 细胞的发育和存活，从而促进血癌的扩散和治疗耐药性的发展。 其中，APRIL 与 MM 的开发相关，而 BAFF 与 DLBCL 相关。

BCMA is a B cell surface receptor that binds to both APRIL and BAFF. Miao and colleagues investigated whether a soluble version of BCMA, unattached to the B cell surface, would act as a “decoy receptor” to mop up excess APRIL and BAFF and prevent these proteins from driving the growth of cancerous B cells.

BCMA 是一种 B 细胞表面受体，可与 APRIL 和 BAFF 结合。Miao 及其同事研究了不附着在 B 细胞表面的可溶性BCMA 是否会充当“诱饵受体”来清除过量的 APRIL 和BAFF，并阻止这些蛋白质驱动癌细胞 B 细胞的生长。

The researchers found that soluble BCMA was able to bind to APRIL and inhibit the growth of MM in mice. However, the decoy receptor only bound weakly to BAFF and was therefore unable to reduce the growth of DLBCL.

研究人员发现，可溶性 BCMA 能够与 APRIL 结合并抑制小鼠 MM（多发性骨髓瘤） 的生长。 然而，诱饵受体仅与 BAFF 弱结合，因此无法减少 DLBCL （弥散性大B细胞淋巴癌）的生长。

Miao and colleagues, therefore, engineered a mutant version of soluble BCMA that binds strongly to both APRIL and BAFF. This molecule, dubbed sBCMA-Fc V3, was able to impede the growth of both MM and DLBCL in rodents.

因此，Miao 及其同事设计了一种可溶性 BCMA 的突变版本，它与 APRIL 和 BAFF 都能强烈结合。 这种被称为 sBCMA-Fc V3 的分子能够阻止啮齿动物中 MM 和 DLBCL 的生长。

Notably, sBCMA-Fc V3 also reduced the activity of APRIL and BAFF in cynomolgus monkeys without causing any significant side effects. This suggests that treatment with sBCMA-Fc V3 or similar decoy receptors could be safe and effective in humans.

值得注意的是，sBCMA-Fc V3 还降低了食蟹猴中 APRIL 和 BAFF 的活性，而不会引起任何明显的副作用。 这表明用 sBCMA-Fc V3 或类似的诱饵受体治疗对人类来说可能是安全有效的。

“Collectively, our data support sBCMA-Fc V3 as a clinically viable candidate for the treatment of MM and DLBCL,” Miao says. “The biological functions of BAFF and APRIL are not limited to B cell malignancies but extend to autoimmune disorders and other diseases triggered by pathological B cells, suggesting an even broader clinical indication for sBCMA-Fc V3.”

“总的来说，我们的数据支持 sBCMA-Fc V3 作为治疗 MM 和 DLBCL 的临床可行候选者，”Miao 说。 “BAFF 和 APRIL 的生物学功能不仅限于 B 细胞恶性肿瘤，还扩展到由病理性 B 细胞引发的自身免疫性疾病和其他疾病，这表明 sBCMA-Fc V3 的临床适应症更为广泛。”