Stephenson Regan, Singh Ankur
Meinig School of Biomedical Engineering, Cornell University, Ithaca, USA.
Meinig School of Biomedical Engineering, Cornell University, Ithaca, USA; Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, USA; Graduate Field Faculty of the Immunology & Infectious Disease Program at the College for Veterinary Medicine, Cornell University, Ithaca, USA.
Adv Drug Deliv Rev. 2017 May 15;114:285-300. doi: 10.1016/j.addr.2017.06.010. Epub 2017 Jun 15.
Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure. This review aims to summarize advances in targeting lymphoma, leukemia, and myeloma through both cutting-edge and well established platforms. Current standard of treatment will be reviewed for these malignancies and emphasis will be made on new therapy development in the areas of antibody engineering, epigenetic small molecule inhibiting drugs, vaccine development, and chimeric antigen receptor cell engineering. In addition, platforms for the delivery of these and other drugs will be reviewed including antibody-drug conjugates, micro- and nanoparticles, and multimodal hydrogels. Lastly, we propose that tissue engineered constructs for hematological malignancies are the missing link in targeted drug discovery alongside mouse and patient-derived xenograft models.
血液系统恶性肿瘤表现为淋巴瘤、白血病和骨髓瘤，仍然是社会的一大负担。从初始治疗到无休止的复发相关治疗，社会负担不仅体现在医疗成本方面，还体现在患者生活质量的下降上。随着这些癌症随着时间的推移对每一轮治疗产生耐药性，长期治疗策略已成为控制血液系统恶性肿瘤的标准。因此，持续需要开发新药来对抗耐药性疾病，以延长患者生命，即便无法实现治愈。本综述旨在总结通过前沿和成熟平台靶向淋巴瘤、白血病和骨髓瘤方面的进展。将对这些恶性肿瘤的当前治疗标准进行综述，并重点关注抗体工程、表观遗传小分子抑制药物、疫苗开发和嵌合抗原受体细胞工程等领域的新疗法开发。此外，还将综述这些药物及其他药物的递送平台，包括抗体药物偶联物、微米和纳米颗粒以及多模式水凝胶。最后，我们提出，血液系统恶性肿瘤的组织工程构建体是靶向药物发现中缺失的环节，与小鼠和患者来源的异种移植模型同等重要。
