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多发性骨髓瘤治疗中突变新抗原的鉴定和靶向。

Identification and Targeting of Mutant Neoantigens in Multiple Myeloma Treatment.

机构信息

Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy.

出版信息

Curr Oncol. 2023 Apr 29;30(5):4603-4617. doi: 10.3390/curroncol30050348.

Abstract

Multiple myeloma (MM) is malignant disease characterized by the clonal proliferation of plasma cells in the bone marrow, leading to anemia, immunosuppression, and other symptoms, that is generally hard to treat. In MM, the immune system is likely exposed to neoplasia-associated neoantigens for several years before the tumor onset. Different types of neoantigens have been identified. Public or shared neoantigens derive from tumor-specific modifications often reported in several patients or across diverse tumors. They are intriguing therapeutic targets because they are frequently observed, and they have an oncogenic effect. Only a small number of public neoantigens have been recognized. Most of the neoantigens that have been identified are patient-specific or "private", necessitating a personalized approach for adaptive cell treatment. It was demonstrated that the targeting of a single greatly immunogenic neoantigen may be appropriate for tumor control. The purpose of this review was to analyze the neoantigens present in patients with MM, and to evaluate the possibility of using their presence as a prognostic factor or as a therapeutic target. We reviewed the most recent literature on neoantigen treatment strategies and on the use of bispecific, trispecific, and conjugated antibodies for the treatment of MM. Finally, a section was dedicated to the use of CAR-T in relapsed and refractory patients.

摘要

多发性骨髓瘤(MM)是一种恶性疾病,其特征是骨髓中浆细胞的克隆性增殖,导致贫血、免疫抑制和其他症状,通常难以治疗。在 MM 中,免疫系统在肿瘤发生前可能会接触到与肿瘤相关的新抗原数年。已经确定了不同类型的新抗原。公共或共享的新抗原源自经常在多个患者或多种肿瘤中报道的肿瘤特异性修饰。它们是有趣的治疗靶点,因为它们经常被观察到,并且具有致癌作用。只有少数公共新抗原得到了认可。大多数已确定的新抗原是患者特异性的或“私有”的,需要针对适应性细胞治疗的个性化方法。已经证明,靶向单个高度免疫原性的新抗原可能适合肿瘤控制。本综述的目的是分析 MM 患者中的新抗原,并评估将其存在用作预后因素或治疗靶点的可能性。我们回顾了关于新抗原治疗策略以及使用双特异性、三特异性和缀合抗体治疗 MM 的最新文献。最后,专门讨论了 CAR-T 在复发和难治性患者中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be11/10217221/ca2ab2d1d9ce/curroncol-30-00348-g001.jpg

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