决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Development of immune cell delivery system using biodegradable injectable polymers for cancer immunotherapy.
使用可注射水凝胶递送免疫细胞以提升其治疗效果备受关注。
利用可注射水凝胶递送免疫细胞以提升其治疗效果备受关注。具体而言,树突状细胞(DCs)是免疫应答的触发细胞,DC疫苗正被研究用于改善癌症免疫治疗。水凝胶辅助的细胞递送有望增强植入细胞的活力。我们近期报道了一种温度响应型可生物降解可注射聚合物(IP)制剂,其利用聚(ε-己内酯-co-乙交酯)-b-聚乙二醇(PEG)-b-聚(ε-己内酯-co-乙交酯)(tri-PCG)。据报道,基于tri-PCG的IP在温度升高时表现出即时溶胶-凝胶转变、体内可生物降解性以及优异的生物相容性。在本研究中,基于tri-PCG的IP被应用于DC递送。IP包封了活性DCs,DCs将卵清蛋白(OVA)作为模型抗原以及CpG-DNA(具有佐剂效应的寡聚DNA)纳入IP水凝胶中。结果表明,包封于IP水凝胶中的DCs内化了OVA和CpG-DNA,且DCs成熟以向T细胞呈递抗原。此外,皮下注射基于tri-PCG的IP延长了细胞在注射部位积聚的保留时间。随着水凝胶逐步降解,tri-PCG IP水凝胶能够释放成熟的DCs。tri-PCG IP制剂提高了OVA转染小鼠淋巴瘤(E.G7-OVA)肿瘤的治疗疗效。因此,tri-PCG IP是一种有前景的免疫细胞递送平台。
Immune cell delivery using injectable hydrogel attracts much attention for improving its therapeutic effect. Specifically, dendritic cells (DCs) are the trigger cells for immune responses, and DC vaccines are studied for improving cancer immunotherapy. Hydrogel-assisted cell delivery is expected to enhance the viability of the implanted cells. We recently reported temperature-responsive biodegradable injectable polymer (IP) formulation utilizing poly(ε-caprolactone-co-glycolide)-b-poly(ethylene glycol)(PEG)-b-poly(ε-caprolactone-co-glycolide) (tri-PCG). Tri-PCG-based IP was reported to exhibit immediate sol-to-gel transition in response to temperature increase, in vivo biodegradability, and excellent biocompatibility. In this study, tri-PCG-based IP was applied to DC delivery. IP encapsulated live DCs, and the DCs incorporated ovalbumin (OVA) as a model antigen and CpG-DNA (oligo DNA with adjuvant effect) in IP hydrogel. Results suggested that DCs encapsulated in IP hydrogel internalized OVA and CpG-DNA and DCs were maturated to present antigens to T cells. Moreover, subcutaneously injected tri-PCG-based IP prolonged the retention period of cell accumulation at injected sites. Tri-PCG IP hydrogel could release matured DCs as the degradation of the hydrogel progressed. Tri-PCG IP formulation improved treatment efficacy of OVA transfected mouse lymphoma (E.G7-OVA) tumor. Hence, tri-PCG IP is a promising platform for immune cell delivery.
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