記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41591-024-03228-8

記述言語：日本語   出版者・発行元：日本小児血液・がん学会  

<p>免疫細胞は腫瘍細胞を認識し殺傷する能力を有することから，がんに対する免疫細胞を用いた細胞療法の開発が進められてきた．本稿では，シンガポール国立大学で実施した細胞療法を中心に紹介する．</p><p>Natural Killer（NK）細胞は，活性化受容体と抑制性受容体のシグナルのバランスにより腫瘍細胞を認識し攻撃するほか，抗体依存性細胞傷害作用や他の免疫細胞の活性化を介して抗腫瘍効果を発揮する．我々は，増殖・活性化させたNK細胞を用いて肉腫に対する臨床試験を実施した．さらに腫瘍特異性を高めるため，腫瘍抗原に対する抗体との併用療法を乳癌や神経芽腫等に対して試みた．これらの臨床試験では一部の被験者に治療反応が認められ，投与された免疫細胞が体内でより長期間持続すれば，治療効果のさらなる向上が期待されることが示唆された．</p><p>治療効果を持続させるため，遺伝子改変技術を用いて膜結合型インターロイキン-15を発現させたNK細胞やFc受容体を含む分子を発現させた自家T細胞を開発した．これらの技術はマウスモデルにおいて，免疫細胞の持続期間の延長による抗腫瘍効果の増強が確認された．</p><p>固形腫瘍における細胞療法の効果は複数の要因により制限されるが，導入遺伝子の改良，複数の腫瘍抗原を標的とする手法，薬剤や放射線との併用，腫瘍微小環境の制御等，種々の戦略が検討されており，今後の開発の進展により，固形腫瘍の予後の改善が期待される．</p>

DOI： 10.11412/jspho.62.214

CiNii Research

Web of Science

記述言語：英語   出版者・発行元：Cytotherapy  

Background aims: Monocytes, derived from hematopoietic stem cells (HSCs), play a pivotal role in the immune response to cancer. Although they are an attractive source of cell therapy for cancer, a method for ex vivo expansion has not yet been established. Monocytes differentiated from pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs), can be an alternative source of HSC-derived monocytes because of their self-renewal and pluripotency. To develop a standardized method for the generation of iPSC-derived monocytes for future clinical applications, we aim to control the size of the iPSC colony. Methods: To this end, we developed a plate with multiple dots containing a chemical substrate for the iPSC scaffold. iPSCs placed in the plate expanded only on the dots and created colonies of the same size. The cells were then differentiated into monocytes by adding cytokines to the colonies. Results: The dot plate substantially reduced variability in monocyte-like cell generation when compared with cultivating cells on a plate with the substrate covering the entire surface area. Furthermore, more monocyte-like cells were obtained by adjusting the dot size and the distance between the dots. The iPSC-derived monocyte-like cells phagocytosed cancer cells and secreted proinflammatory cytokines. The cells also expressed Fc receptors and exerted immunoglobulin G-mediated killing of cancer cells with the corresponding antibodies. Conclusions: The dot plate enabled the control of iPSC colony size in two-dimensional culture, which resulted in a reduction in the generation-variation of functional monocyte-like cells. This standardized method for generating iPSC-derived monocyte-like cells using the dot plate could also facilitate the development of an automated closed system on a large scale for clinical applications.

DOI： 10.1016/j.jcyt.2023.08.002

Web of Science

Scopus

PubMed

DOI： 10.1182/blood-2023-189160

Web of Science