T细胞重定向双特异性抗体:一类治疗晚期前列腺癌的新型免疫肿瘤学综述。

IF 4.6 4区 医学 Q2 ONCOLOGY Cancer Biology & Therapy Pub Date : 2024-12-31 Epub Date: 2024-05-27 DOI:10.1080/15384047.2024.2356820
Julia Palecki, Amman Bhasin, Andrew Bernstein, Patrick J Mille, William J Tester, Wm Kevin Kelly, Kevin K Zarrabi
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引用次数: 0

摘要

新型 T 细胞免疫疗法,如双特异性 T 细胞吞噬体(BiTEs),正逐渐成为治疗前列腺癌的有效策略。BiTEs 是一种工程化的双特异性抗体,含有两个不同的结合域,可同时与肿瘤相关抗原(TAAs)和免疫效应细胞结合,从而促进针对癌细胞的免疫反应。前列腺癌富含肿瘤相关抗原,如但不限于 PSMA、PSCA、hK2 和 STEAP1,因此在前列腺癌疾病领域使用 T 细胞重定向 BiTE 具有很强的生物学依据。临床研究中使用的第一代 BiTE 构建物已显示出有意义的抗肿瘤活性,但与给药、免疫原性和治疗相关的不良反应有关的挑战限制了它们的成功。目前,新型生物TE 构建物的开发工作正在继续解决这些障碍,并在疗效和安全性方面取得了可喜的成果。本综述将重点介绍针对晚期前列腺癌患者的生物TE疗法的一些最新进展,以及围绕正在接受临床评估的生物TE构建物不断变化的数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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T-Cell redirecting bispecific antibodies: a review of a novel class of immuno-oncology for advanced prostate cancer.

Novel T-cell immunotherapies such as bispecific T-cell engagers (BiTEs) are emerging as promising therapeutic strategies for prostate cancer. BiTEs are engineered bispecific antibodies containing two distinct binding domains that allow for concurrent binding to tumor-associated antigens (TAAs) as well as immune effector cells, thus promoting an immune response against cancer cells. Prostate cancer is rich in tumor associated antigens such as, but not limited to, PSMA, PSCA, hK2, and STEAP1 and there is strong biologic rationale for employment of T-cell redirecting BiTEs within the prostate cancer disease space. Early generation BiTE constructs employed in clinical study have demonstrated meaningful antitumor activity, but challenges related to drug delivery, immunogenicity, and treatment-associated adverse effects limited their success. The ongoing development of novel BiTE constructs continues to address these barriers and to yield promising results in terms of efficacy and safety. This review will highlight some of most recent developments of BiTE therapies for patients with advanced prostate cancer and the evolving data surrounding BiTE constructs undergoing clinical evaluation.

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来源期刊
Cancer Biology & Therapy
Cancer Biology & Therapy 医学-肿瘤学
CiteScore
7.00
自引率
0.00%
发文量
60
审稿时长
2.3 months
期刊介绍: Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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