单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肽-MHC 靶向逆转录病毒可实现体内扩增并向肿瘤特异性 T 细胞递送基因
英文原题：Peptide-MHC-targeted retroviruses enable in vivo expansion and gene delivery to tumor-specific T cells.
查看英文原题
Peptide-MHC-targeted retroviruses enable in vivo expansion and gene delivery to tumor-specific T cells.
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中文摘要
TIL（肿瘤浸润淋巴细胞）疗法已证明可以利用内源性T细胞启动有效的抗肿瘤反应。尽管具有临床前景，但当前的TIL生产方案涉及长达数周的体外扩增，这可能影响治疗效果。因此，需要额外的工具来改造TIL，使其具有更强的效力，同时减轻生产挑战。在此，我们提出了一种用肽-主要组织相容性复合体（pMHC）假型化逆转录病毒的策略，用于向CD8 T细胞进行抗原特异性基因递送，并在免疫活性小鼠模型中验证了治疗效果。我们证明，pMHC靶向病毒能够特异性递送增强功能的载荷，同时激活和扩增抗肿瘤T细胞。这种靶向精确性使得能够在体内工程化肿瘤特异性T细胞，从而改善B16F10荷瘤小鼠的总生存期。总之，我们已证实pMHC靶向病毒是直接在体内重编程和扩增肿瘤特异性T细胞的高效载体，具有大幅简化工程化细胞疗法生产的潜力。
展开英文摘要原文
Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated that endogenous T cells can be harnessed to initiate effective antitumor responses. Despite clinical promise, current TIL production protocols involve weeks-long ex vivo expansions that can affect treatment efficacy.
Therefore, additional tools are needed to engineer TILs to have increased potency while mitigating manufacturing challenges.
Here, we present a strategy for pseudotyping retroviruses with peptide-major histocompatibility complexes (pMHCs) for antigen-specific gene delivery to CD8 T cells and validate therapeutic impact in immunocompetent mouse models.
We demonstrate that pMHC-targeted viruses specifically deliver function-enhancing cargos while simultaneously activating and expanding antitumor T cells. This targeting precision enables in vivo engineering of tumor-specific T cells, resulting in improved overall survival in B16F10-bearing mice.
Together, we have established that pMHC-targeted viruses are efficient vectors for reprogramming and expanding tumor-specific T cells directly in vivo, with the potential to substantially streamline engineered cell therapy production.
论文信息
- 作者
- Xu EJK、Smith BE、Conce Alberto WD、Walsh MJ、Lim B、Hoffman MT、Qiang L、Barreiro A
- 单位
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.United Kingdom
- 文献类型
- 非美国政府资助研究 · 美国 NIH 资助研究
- 期刊
- Science advances2025 Nov 7
- 原文标识
- PubMed 41202121 · DOI 10.1126/sciadv.adv2331
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