Advances in Immunotherapy for the Treatment of Adult Glioblastoma: Overcoming Chemical and Physical Barriers.
Advances in Immunotherapy for the Treatment of Adult Glioblastoma: Overcoming Chemical and Physical Barriers.
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DOI：
10.3390/cancers14071627
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发表时间：
2022-03-23
期刊：
影响因子：
5.2
通讯作者：
Sengupta S
中科院分区：
文献类型：
--
作者：
Lechpammer M;Rao R;Shah S;Mirheydari M;Bhattacharya D;Koehler A;Toukam DK;Haworth KJ;Pomeranz Krummel D;Sengupta S
胶质母细胞瘤（GBM）的预后差，尽管存在的标准治疗切除术，放疗和辅助化疗，有必要探索其他治疗途径。一个特别有前途的途径是免疫学方法，其中人体的免疫系统被人工刺激以直接识别和攻击肿瘤细胞。正在开发多种方法用于GBM，包括免疫检查点抑制、T细胞转移、疫苗接种和病毒方法。诸如肿瘤异质性、物理血脑屏障、GBM的免疫抑制性质以及可识别的GBM特异性靶标的有限数量的屏障已经降低了上述方法的功效。在下面的综述中，我们记录了免疫治疗的进展，实施的障碍，以及一种新技术（微泡增强聚焦超声）的发展，以克服免疫治疗的物理障碍。胶质母细胞瘤或多形性胶质母细胞瘤（GBM，WHO IV级）是一种高度侵袭性的成人胶质瘤。尽管广泛的努力，以改善治疗，目前的标准治疗（SOC）方案，其中包括最大的切除，放疗和替莫唑胺（TMZ），实现只有12-15个月的生存期。通过免疫疗法在几种颅外实体瘤（包括非小细胞肺癌、黑色素瘤和非霍奇金淋巴瘤）中实现的临床改善激发了对成人胶质母细胞瘤患者进行各种免疫干预的研究。尽管有一些令人鼓舞的报告，从临床前和早期临床试验，没有一个测试的代理人已令人信服的III期临床试验。其中一个但不是唯一的原因是血脑屏障，它阻止大多数抗肿瘤药物以可观的数量到达目标。在此，我们回顾了胶质母细胞瘤免疫治疗的现状，并讨论了阻止进展的重大挑战。我们还提供了可能采取的措施来解决这些挑战的想法，包括超声技术的应用。
The poor prognosis for glioblastoma (GBM) despite the existence of a standard-of-care treatment of resection, radiotherapy, and adjuvant chemotherapy has necessitated the exploration of other therapeutic avenues. One particularly promising avenue is an immunotherapeutic approach in which the body′s immune system is artificially stimulated to directly identify and attack the tumor cells. A variety of methods including immune checkpoint inhibition, T-cell transfer, vaccination, and a viral approach are being developed for GBM. Barriers such as tumor heterogeneity, the physical blood–brain barrier, the immunosuppressive nature of GBM, and the limited number of identifiable GBM-specific targets have reduced the efficacy of the aforementioned approaches. In the following review, we document the advances in immunotherapy, the barriers to implementation, and the development of a new technology (microbubble-enhanced focused ultrasound) to overcome the physical barriers to immunotherapy. Glioblastoma, or glioblastoma multiforme (GBM, WHO Grade IV), is a highly aggressive adult glioma. Despite extensive efforts to improve treatment, the current standard-of-care (SOC) regimen, which consists of maximal resection, radiotherapy, and temozolomide (TMZ), achieves only a 12–15 month survival. The clinical improvements achieved through immunotherapy in several extracranial solid tumors, including non-small-cell lung cancer, melanoma, and non-Hodgkin lymphoma, inspired investigations to pursue various immunotherapeutic interventions in adult glioblastoma patients. Despite some encouraging reports from preclinical and early-stage clinical trials, none of the tested agents have been convincing in Phase III clinical trials. One, but not the only, factor that is accountable for the slow progress is the blood–brain barrier, which prevents most antitumor drugs from reaching the target in appreciable amounts. Herein, we review the current state of immunotherapy in glioblastoma and discuss the significant challenges that prevent advancement. We also provide thoughts on steps that may be taken to remediate these challenges, including the application of ultrasound technologies.
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影响因子：
2.6
作者：
Banks WA
通讯作者：
Banks WA
影响因子：
4.1
作者：
Asquier, Nicolas;Bouchoux, Guillaume;Carpentier, Alexandre
通讯作者：
Carpentier, Alexandre
影响因子：
15.9
作者：
Alkins, Ryan;Burgess, Alison;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo
DOI：
10.1016/j.jconrel.2013.04.007
发表时间：
2013-07-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Aryal M;Vykhodtseva N;Zhang YZ;Park J;McDannold N
通讯作者：
McDannold N
DOI：
10.1016/j.jconrel.2018.05.005
发表时间：
2018-07-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Alli S;Figueiredo CA;Golbourn B;Sabha N;Wu MY;Bondoc A;Luck A;Coluccia D;Maslink C;Smith C;Wurdak H;Hynynen K;O'Reilly M;Rutka JT
通讯作者：
Rutka JT