Masmudur Rahman is a researcher in the Biodesign Center for Immunotherapy, Vaccines and Virotherapy. Credit: The Biodesign Institute at Arizona State University

Masmudur Rahman 是免疫疗法、疫苗和病毒疗法生物设计中心的研究员。 图片来源：亚利桑那州立大学生物设计研究所

Through a range of evasive strategies, cancer cells can further short-circuit immune efforts to hunt and destroy them. Scientists hope to help the immune system to overcome cancer’s notorious tactics of disguise, by developing new experimental techniques belonging to a category known as adoptive cell therapy, or ACT.

通过一系列规避策略，癌细胞可以进一步缩短免疫努力来猎杀和摧毁它们。 科学家们希望通过开发属于过继细胞疗法（ACT）的新实验技术，帮助免疫系统克服癌症臭名昭著的伪装策略。

Such methods often involve extracting a collection of cancer-fighting white blood cells known as T-cells, modifying their seek-and-destroy capacities, and reinjecting them in patients. Two forms of ACT immunotherapy are described in the new study: CAR T-cell therapy (CART) and T Cell Receptor Engineering (TCR). In each case the basic idea is the same: treating cancer with activated T lymphocytes extracted from the patient.

这种方法通常涉及提取一组称为 T 细胞的抗癌白细胞，改变它们的寻找和破坏能力，并将它们重新注入患者体内。 新研究中描述了两种形式的 ACT 免疫疗法：CAR T 细胞疗法 (CART) 和 T 细胞受体工程 (TCR)。 在每种情况下，基本思想都是相同的：用从患者身上提取的活化T 淋巴细胞来治疗癌症。

New method delivers a one-two punch to tumor cells

The development of these therapies has been nothing short of revolutionary. In fact, some cancer patients facing grim prospects have made remarkable recoveries following the use of immunotherapy. However, techniques like CART and TCR nevertheless have their limitations and are frequently ineffective against advanced solid tumors. In such cases, cancer cells often manage to evade destruction by T-cells by downregulating or losing the surface antigens or MHC proteins that T-cells use to identify them.

新方法对肿瘤细胞进行一两次打击

这些疗法的发展简直是革命性的。 事实上，一些面临严峻前景的癌症患者在使用免疫疗法后已经取得了显着的康复。 然而，像 CART 和 TCR 这样的技术仍然有其局限性，并且通常对晚期实体瘤无效。 在这种情况下，癌细胞通常通过下调或丢失 T 细胞用来识别它们的表面抗原或MHC 蛋白来设法逃避 T 细胞的破坏。

The new research highlights the ability of immunotherapy when it is coupled with virotherapy to break through the wall of cancer resistance, specifically using myxoma-equipped T-cells. The myxoma can target and kill cancer cells directly, but more usefully, can induce an unusual form of T-cell-directed cell death known as autosis. This form of cell death augments two other forms of programmed cancer cell death induced by T-cells, known as apoptosis and pyroptosis.

这项新研究强调了免疫疗法与病毒疗法相结合时突破癌症抗性壁的能力，特别是使用配备粘液瘤的 T 细胞。 粘液瘤可以直接靶向和杀死癌细胞，但更有用的是，它可以诱导一种不寻常的 T 细胞定向细胞死亡，称为自体症。 这种形式的细胞死亡增强了由 T 细胞诱导的两种其他形式的程序性癌细胞死亡，即细胞凋亡和细胞焦亡。

During myxoma-mediated autosis, cancerous cells in the proximity of those targeted by the therapy are also destroyed in a process known as bystander killing. This effect can considerably enhance the dual therapy’s aggressive eradication of cancer cells, even in notoriously hard-to-treat solid tumors.

在粘液瘤介导的自闭症期间，治疗目标附近的癌细胞也在被称为旁观者杀伤的过程中被破坏。 这种效果可以显着增强双重疗法对癌细胞的积极根除，即使是在臭名昭著的难以治疗的实体瘤中也是如此。

A combined myxoma-immunotherapy approach, therefore, holds the potential to turn so-called “cold tumors,” which fly under the immune system’s radar, into “hot tumors” that immune cells can identify and destroy, allowing CAR T-cells or TCR cells to enter the tumor environment, proliferate and activate.

因此，一种联合粘液瘤免疫疗法有可能将在免疫系统雷达下飞行的所谓“冷肿瘤”转变为免疫细胞可以识别和破坏的“热肿瘤”，从而允许 CAR T 细胞或 TCR 细胞进入肿瘤环境，增殖并激活。

“We are at the edge of discovering newer aspects of the myxoma virus and oncolytic virotherapy,” Rahman says. “In addition, these findings open the door for testing cancer-killing viruses with other cell-based cancer immunotherapies that can be used in cancer patients.”

“我们正处于发现粘液瘤病毒和溶瘤病毒疗法的新方面的边缘，”拉赫曼说。 “此外，这些发现为使用其他可用于癌症患者的基于细胞的癌症免疫疗法测试抗癌病毒打开了大门。”

A new frontier for the treatment of this devastating disease is rising with the ability to radically reengineer oncolytic viruses like myxoma to target a range of resistant cancers.

治疗这种毁灭性疾病的新前沿正在兴起，能够从根本上重新设计溶瘤病毒（如粘液瘤）以靶向一系列耐药性癌症。