Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI:10.1007/s00262-024-03817-z
Marat Khaliulin, Aygul Valiullina, Alexey Petukhov, Youyong Yuan, Sheila Spada, Emil Bulatov
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Abstract

The use of chimeric antigen receptor (CAR)-T cells has enhanced the range of available therapeutic modalities in the context of cancer treatment. CAR-T cells have demonstrated considerable efficacy in the targeted eradication of blood cancer cells, thereby stimulating substantial interest in the advancement of such therapeutic approaches. However, the efficacy of CAR-T cells against solid tumor cells has been limited due to the presence of various obstacles. Solid tumors exhibit antigenic diversity and an immunosuppressive microenvironment, which presents a challenge for immune cells attempting to penetrate the tumor. CAR-T cells also demonstrate decreased proliferative activity and cytotoxicity. Furthermore, concerns exist regarding tumor antigen loss and therapy-associated toxicity. Currently, scientists are working to enhance the structure of the CAR and improve the survival and efficiency of CAR-T cells in recognizing tumor antigens in solid tumors. Chemotherapy drugs are frequently employed in the treatment of malignant neoplasms and can also be used prior to cell therapy to enhance CAR-T cell engraftment. Recent studies have demonstrated that chemotherapy drugs can mitigate the suppressive impact of TME, eliminate the physical barrier by destroying the tumor stroma, and facilitate greater penetration of immune cells and CAR-T cells into the tumor. This, in turn, increases their survival, persistence, and cytotoxicity, as well as affects the metabolism of immune cells inside the tumor. However, the effectiveness of the combined approach against solid tumors depends on several factors, including the type of tumor, dosage, population of CAR-T cells, and individual characteristics of the body. This review examines the principal obstacles to the utilization of CAR-T cells against solid tumors, proposes solutions to these issues, and assesses the potential advantages of a combined approach to radiation exposure, which has the potential to enhance the sensitivity of the tumor to other agents.

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打破实体肿瘤的防护罩:增强 CAR-T 细胞疗效的综合方法。
嵌合抗原受体(CAR)-T 细胞的使用扩大了癌症治疗的可用治疗方法范围。CAR-T 细胞在有针对性地根除血癌细胞方面已显示出相当大的疗效,从而激发了人们对推进此类治疗方法的浓厚兴趣。然而,由于存在各种障碍,CAR-T 细胞对实体瘤细胞的疗效受到了限制。实体瘤表现出抗原多样性和免疫抑制微环境,这给试图穿透肿瘤的免疫细胞带来了挑战。CAR-T 细胞的增殖活性和细胞毒性也有所下降。此外,肿瘤抗原丢失和治疗相关毒性也令人担忧。目前,科学家们正在努力增强 CAR 的结构,提高 CAR-T 细胞的存活率和识别实体瘤中肿瘤抗原的效率。化疗药物是治疗恶性肿瘤的常用药物,也可在细胞治疗前使用,以提高 CAR-T 细胞的接种率。最近的研究表明,化疗药物可减轻TME的抑制作用,通过破坏肿瘤基质消除物理屏障,促进免疫细胞和CAR-T细胞更好地穿透肿瘤。这反过来又会提高它们的存活率、持久性和细胞毒性,并影响肿瘤内免疫细胞的新陈代谢。然而,联合疗法对实体瘤的疗效取决于多种因素,包括肿瘤类型、剂量、CAR-T 细胞的数量以及机体的个体特征。这篇综述探讨了利用 CAR-T 细胞治疗实体瘤的主要障碍,提出了解决这些问题的方法,并评估了辐射照射联合方法的潜在优势,因为这种方法有可能提高肿瘤对其他药物的敏感性。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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