Research press release


Nature Biotechnology

Making tumor-targeting T cells in a dish



今回、Michel Sadelainたちは、この2つの方法を組み合わせることで、腫瘍特異的T細胞を無制限に培養でき、そのT細胞がマウスの腫瘍を抑制できることを明らかにした。Sadelainたちは、健常者の血液から単離した少量のT細胞を出発材料として用い、それを幹細胞へ再プログラム化し、この幹細胞を操作して、腫瘍特異的受容体を発現させた。この幹細胞は、当初のT細胞の特性を再び獲得できるように誘導され、大量に増やされた後、腫瘍を持つマウスに注入された。Sadelainたちは、実験室で作製されたT細胞によるマウスの腫瘍増殖の抑制効果が、同じ提供者の血液から単離され、同じ腫瘍特異的受容体を発現するように操作された自然のT細胞の場合と類似していることを見いだした。この方法が臨床的に応用されれば、この種のがん免疫療法を受けられる患者の数がかなり増える可能性がある。

A method for producing from stem cells a large quantity of human immune cells capable of killing tumor cells in mice is presented in a paper published online this week in Nature Biotechnology. The approach may make it easier to implement cancer ‘immunotherapies’-a suite of treatments that activate the immune system to attack tumors.

Most cancer immunotherapy strategies require isolation of immune cells called T cells from the blood of cancer patients. However, T cells that specifically recognize and kill only tumor cells but not healthy cells are very rare, and the problem is how to generate large numbers of such cells. Previous work has shown that either T cells can be engineered to express tumor-specific receptors or they can be grown in large numbers using ‘reprogramming’ technology.

Now, Michel Sadelain and colleagues combined these methods to grow an unlimited supply of tumor-specific T cells and demonstrated the ability of the cells to control tumors in mice. The authors started with a small number of T cells isolated from the blood of a healthy person, reprogrammed the cells into stem cells, and engineered the stem cells to express a tumor-specific receptor. The stem cells were coaxed to reacquire their original T cell properties, expanded to large numbers, and then injected into tumor-bearing mice. Sadelain and colleagues found that the lab-grown T cells suppressed tumor growth in the mice to an extent similar to that of natural T cells that were isolated from the blood of the same person and engineered to express the same tumor-specific receptor. If the approach can be translated to the clinic, many more patients could become eligible to receive this type of cancer immunotherapy.

doi: 10.1038/nbt.2678


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