肿瘤细胞治疗研究
英文原题：Functionalizing Hydrogel Nanovials with Vesicles Mimicking Antigen-Presenting Vesicles and Cancer Exosomes Improves T Cell Capture and Activation.
近期进展已证明，含微腔的水凝胶微粒（称为 nanovials）可用于对过继性细胞治疗所用的治疗性 T 细胞群体进行大规模并行、高通量筛选。
近期研究已证明，含微腔的水凝胶微粒（称为 nanovial）可用于大规模、高通量筛选过继性细胞治疗所需的治疗性 T 细胞群。纳米微粒腔体涂覆肽-MHC（pMHC）或抗原四聚体后，可选择性结合相应的 T 细胞受体（TCR）或嵌合抗原受体（CAR），从而激活 T 细胞并捕获其分泌的细胞因子。然而，T 细胞对四聚体或重组表达抗原的结合，未必能反映生理状态下的 T 细胞活化或细胞毒性，因为这种结合界面并不能充分模拟 T 细胞与专业抗原呈递细胞（APC）之间形成的天然免疫突触。本研究利用近期发现的 ESCRT 和 ALIX 结合区域（EABR）序列，从常规 HEK293T 和 Expi293F 细胞培养物中制备抗原呈递囊泡及模拟肿瘤的外泌体。EABR 介导的囊泡将天然、全长且与肿瘤相关的膜蛋白呈递于脂质双层中，使纳米微粒腔体表面具备类细胞膜特征。与涂覆重组可溶性蛋白的水凝胶表面相比，采用 EABR 囊泡功能化的水凝胶纳米微粒提高了对 1G4 T 细胞的捕获，并增强了 HER2 CAR-T 细胞的分泌诱导。
Recent advances have demonstrated the application of microcavity-containing hydrogel microparticles, known as nanovials, for massively parallel and high-throughput screening of therapeutic T cell populations for adoptive cell therapies. Nanovial cavities coated with peptide-MHC (pMHC) or antigen tetramers selectively bind to their cognate T cell receptor (TCR) or chimeric antigen receptor (CAR) to activate T cells and capture secreted cytokines. However, binding of tetramers or recombinantly expressed antigen by T cells may not reflect physiological T cell activation or cytotoxicity, as the binding interface is not fully representative of the natural immunological synapse formed between T cells and professional antigen-presenting cells (APCs). Here, we leverage the recent discovery of an ESCRT- and ALIX-binding region (EABR) sequence to generate antigen-presenting vesicles and cancer-mimicking exosomes from standard HEK293T and Expi293F cell cultures. EABR-mediated vesicles present natural, full-length oncologically relevant membrane proteins embedded in lipid bilayers to functionalize the nanovial cavity with cell-like membranes. Hydrogel nanovials functionalized with the EABR-mediated vesicles show improved T cell capture of 1G4 T cells and enhanced induction of secretion in HER2 CAR-T cells compared to hydrogel surfaces functionalized with recombinantly expressed soluble proteins.
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