Gardner Thomas J, Bourne Christopher M, Dacek Megan M, Kurtz Keifer, Malviya Manish, Peraro Leila, Silberman Pedro C, Vogt Kristen C, Unti Mildred J, Brentjens Renier, Scheinberg David
Molecular Pharmacology Program, Sloan Kettering Institute, New York, NY 10065, USA.
Immunology Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
Cancers (Basel). 2020 Aug 5;12(8):2175. doi: 10.3390/cancers12082175.
The recent emergence of engineered cellular therapies, such as Chimeric antigen receptor (CAR) CAR T and T cell receptor (TCR) engineered T cells, has shown great promise in the treatment of various cancers. These agents aggregate and expand exponentially at the tumor site, resulting in potent immune activation and tumor clearance. Moreover, the ability to elaborate these cells with therapeutic agents, such as antibodies, enzymes, and immunostimulatory molecules, presents an unprecedented opportunity to specifically modulate the tumor microenvironment through cell-mediated drug delivery. This unique pharmacology, combined with significant advances in synthetic biology and cell engineering, has established a new paradigm for cells as vectors for drug delivery. Targeted cellular micropharmacies (TCMs) are a revolutionary new class of living drugs, which we envision will play an important role in cancer medicine and beyond. Here, we review important advances and considerations underway in developing this promising advancement in biological therapeutics.
近年来出现的工程细胞疗法,如嵌合抗原受体(CAR)CAR-T细胞和工程化T细胞受体(TCR)T细胞,在治疗各种癌症方面显示出巨大的前景。这些药物在肿瘤部位聚集并呈指数级扩增,从而产生强大的免疫激活和肿瘤清除作用。此外,用治疗剂(如抗体、酶和免疫刺激分子)对这些细胞进行修饰的能力,为通过细胞介导的药物递送特异性调节肿瘤微环境提供了前所未有的机会。这种独特的药理学特性,再加上合成生物学和细胞工程的重大进展,为细胞作为药物递送载体建立了新的范例。靶向细胞微型药房(TCM)是一类革命性的新型活体药物,我们设想它将在癌症医学及其他领域发挥重要作用。在此,我们回顾了在这一有前景的生物治疗进展方面正在取得的重要进展和需要考虑的因素。