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经基因工程改造以表达抗人乳头瘤病毒(HPV)抗体的小鼠B细胞可引发抗肿瘤T细胞反应。

Mouse B cells engineered to express an anti-HPV antibody elicit anti-tumor T cell responses.

作者信息

Guberman Bracha Michal, Biber Guy, Zelikson Natalie, Shavit Sharon, Avraham Roy, Vagima Yaron, Bublik Débora Rosa, Katz Yael, Barzel Adi, Klapper Leah Natasha, Hess Shmuel, Nahmad Alessio David

机构信息

Tabby Therapeutics Ltd, Ness Ziona, Israel.

Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

出版信息

Front Immunol. 2025 Jul 18;16:1613879. doi: 10.3389/fimmu.2025.1613879. eCollection 2025.

DOI:10.3389/fimmu.2025.1613879
PMID:40755763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12313569/
Abstract

Transplantation of engineered B cells has demonstrated efficacy in HIV disease models. B cell engineering may also be utilized for the treatment of cancer. Recent studies have highlighted that B cell activity is associated with favorable clinical outcomes in oncology. In mice, polyclonal B cells have been shown to elicit anti-cancer responses. As a potential novel cell therapy, we demonstrate that engineering B cells to target a tumor-associated antigen enhances polyclonal anti-tumor responses. We observe that engineered B cells expressing an anti-HPV B cell receptor internalize the antigen, enabling subsequent activation of oncoantigen-specific T cells. Secreted antibodies from engineered B cells form immune complexes, which are taken up by antigen-presenting cells to further promote T cell activation. Engineered B cells hold promise as novel, multi-modal cell therapies and open new avenues in solid tumor targeting.

摘要

工程化B细胞移植已在HIV疾病模型中显示出疗效。B细胞工程也可用于癌症治疗。最近的研究强调,B细胞活性与肿瘤学中良好的临床结果相关。在小鼠中,多克隆B细胞已被证明能引发抗癌反应。作为一种潜在的新型细胞疗法,我们证明将B细胞工程化以靶向肿瘤相关抗原有助于增强多克隆抗肿瘤反应。我们观察到,表达抗HPV B细胞受体的工程化B细胞会内化抗原,从而激活癌抗原特异性T细胞。工程化B细胞分泌的抗体形成免疫复合物,被抗原呈递细胞摄取,进一步促进T细胞激活。工程化B细胞有望成为新型多模式细胞疗法,并为实体瘤靶向治疗开辟新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/f540d5d4ec5f/fimmu-16-1613879-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/3eb83a2d13b1/fimmu-16-1613879-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/db68188032c5/fimmu-16-1613879-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/088cb992f424/fimmu-16-1613879-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/b3fd7c15c6a7/fimmu-16-1613879-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/f540d5d4ec5f/fimmu-16-1613879-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/3eb83a2d13b1/fimmu-16-1613879-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/db68188032c5/fimmu-16-1613879-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/088cb992f424/fimmu-16-1613879-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/b3fd7c15c6a7/fimmu-16-1613879-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/12313569/f540d5d4ec5f/fimmu-16-1613879-g005.jpg

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Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers.用于实体癌患者的白细胞介素-15武装的GPC3嵌合抗原受体T细胞。
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Single-hit genome editing optimized for maturation in B cells redirects their specificity toward tumor antigens.
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