借力推动前列腺癌 CAR-T 细胞治疗进展
Piggybacking toward Progress for CAR T-Cell Therapy in Prostate Cancer.
P-PSMA-101 是一款首创的、富集干细胞记忆 T 细胞的、靶向前列腺特异性膜抗原(PSMA)的嵌合抗原受体(CAR)T 疗法。
英文原题:In situ generation of dendritic cell vaccines in 3D printing scaffolds for cancer post-surgical therapy.
树突状细胞(DC)疫苗在肿瘤治疗中展现出巨大潜力,而复杂的体外细胞培养限制了其临床应用。
树突状细胞(DC)疫苗在肿瘤治疗中展现出巨大潜力,但复杂的体外细胞培养限制了其临床应用。在此,我们报道了一种原位生成的支架DC疫苗,由简单的3D打印明胶甲基丙烯酰、骨髓单核细胞(BM-MNCs)、肿瘤裂解物和刺激因子组成。该疫苗中的刺激因子有效启动了BM-MNCs原位分化为DCs,而个性化肿瘤裂解物则刺激了分化DCs的成熟并增强了其淋巴结迁移效率,从而协同增强其抗肿瘤效应。此外,3D水凝胶支架作为原位细胞培养基质,促进了包封细胞的长期存活,并为手术床内BM-MNC分化和DC成熟提供了有利环境。在前列腺癌术后小鼠模型中,该疫苗显著抑制了肿瘤生长,抑制了肿瘤转移,并将动物的中位生存期延长至55天。这种原位生成的DC疫苗绕过了体外细胞培养,为激发抗肿瘤免疫以治疗癌症提供了一种简单、安全且稳健的策略。
Dendritic cell (DC) vaccines have shown great promise in cancer management, while complex ex vivo cell culture limits their clinical applications. Here, we report an in situ -generated scaffold DC vaccine, comprising a simple 3D-printed gelatin methacryloyl, bone marrow mononuclear cells (BM-MNCs), tumor lysates and stimulating factors. Stimulating factors in this vaccine effectively initiated in situ differentiation of BM-MNCs into DCs, while personalized tumor lysates stimulated the maturation of differentiated DCs and enhanced their lymph node migration efficiency, thereby synergistically strengthening their antitumor effects. Moreover, the 3D hydrogel scaffold serves as an in situ cell culture matrix, promoting the long-term viability of encapsulated cells and providing a conducive environment for BM-MNC differentiation and DC maturation within the surgical bed. In a prostate cancer post-surgical mouse model, the vaccine significantly inhibited tumor growth, suppressed tumor metastasis and extended median survival of animals to 55 days. This in situ -generated DC vaccine bypasses ex vivo cell culture, offering a simple, safe and robust strategy to elicit antitumor immunity for cancer treatment.
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