美國哥倫比亞大學(xué)Tal Danino團隊提出益生菌引導(dǎo)的嵌合抗原受體(CAR)-T細胞靶向?qū)嶓w腫瘤。2023年10月13日出版的《科學(xué)》雜志發(fā)表了這項成果。
他們開發(fā)了一種益生菌引導(dǎo)的CAR-T細胞(ProCARs)平臺,在該平臺中,腫瘤定殖的益生菌釋放合成靶標,標記腫瘤組織以進行CAR介導(dǎo)的原位溶解。該系統(tǒng)證明了CAR-T細胞活化和抗原不加區(qū)分的細胞溶解,在人類和小鼠癌癥的多種異種移植和同基因模型中是安全有效的。他們進一步設(shè)計多功能益生菌,共同釋放趨化因子,以增強CAR-T細胞募集和治療反應(yīng)。
研究人員表示,腫瘤抗原靶向療法,如CAR-T細胞面臨的一個主要挑戰(zhàn)是識別在異質(zhì)性固體腫瘤上具體和一致表達的適當靶點。與此相反,某些細菌種類能夠有選擇性地寄生在免疫特權(quán)的腫瘤核心區(qū)域,并且可以被設(shè)計成抗原無關(guān)的治療遞送平臺。
《科學(xué)》:Volume 382 Issue 6667
附:英文原文
Title: Probiotic-guided CAR-T cells for solid tumor targeting
Author: Rosa L. Vincent, Candice R. Gurbatri, Fangda Li, Ana Vardoshvili, Courtney Coker, Jongwon Im, Edward R. Ballister, Mathieu Rouanne, Thomas Savage, Kenia de los Santos-Alexis, Andrew Redenti, Leonie Brockmann, Meghna Komaranchath, Nicholas Arpaia, Tal Danino
Issue&Volume: 2023-10-13
Abstract: A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)–T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ. This system demonstrated CAR-T cell activation and antigen-agnostic cell lysis that was safe and effective in multiple xenograft and syngeneic models of human and mouse cancers. We further engineered multifunctional probiotics that co-release chemokines to enhance CAR-T cell recruitment and therapeutic response.
來源:科學(xué)網(wǎng)
作者:小柯
北京清美聯(lián)創(chuàng)干細胞科技有限公司致力于多種干細胞臨床應(yīng)用研究,人體冷凍、核輻射防治等技術(shù)研發(fā)。
目前已擁有67種不同功能的專能細胞如神經(jīng)干細胞、胰腺干細胞、卵巢干細胞、肝臟干細胞、心肌細胞、毛囊干細胞等的制備技術(shù)。
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