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多发性骨髓瘤与新型免疫检查点抑制剂的免疫治疗潜力

Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy.

作者信息

Kamali Ali N, Hamedifar Haleh, Eisenhut Michael, Bautista Jose M

机构信息

CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.

CinnaGen Research and Production Co., Alborz, Iran.

出版信息

Ther Adv Vaccines Immunother. 2024 Oct 9;12:25151355241288453. doi: 10.1177/25151355241288453. eCollection 2024.

Abstract

Multiple myeloma (MM), a cancer of the bone marrow, is categorized as the second most common hematological malignancy of adults in the Western world. Despite dramatic improvements in immunotherapies in the field of cancers, MM immunotherapy has not been promising until now. Recent clinical studies of immune checkpoint inhibitor therapy, either alone or in combination with anticancer drugs, showed excessive side effects or low efficacy, particularly in advanced MM patients. In this context, lymphocyte levels of exhaustion markers play a pivotal role in the MM tumor microenvironment (TME). Hence in the present review, the mechanisms relevant to MM of five inhibitory molecules including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin, and mucin domain 3 (Tim-3), lymphocyte activation gene-3 (LAG-3), V-domain Ig Suppressor of T-cell activation and killer immunoglobulin-like receptors along with bispecific T-cell antibodies (BsAbs) will be discussed. Further, we summarized the underlying biology of these checkpoints in cancer and their rapidly emerging role in pathways in MM along with presenting recent clinical trials in context.

摘要

多发性骨髓瘤(MM)是一种骨髓癌,在西方世界被归类为成人中第二常见的血液系统恶性肿瘤。尽管癌症领域的免疫疗法有了显著进展,但迄今为止,MM免疫疗法一直没有取得理想效果。最近关于免疫检查点抑制剂疗法的临床研究,无论是单独使用还是与抗癌药物联合使用,都显示出副作用过大或疗效低下,尤其是在晚期MM患者中。在这种情况下,耗竭标志物的淋巴细胞水平在MM肿瘤微环境(TME)中起着关键作用。因此,在本综述中,将讨论包括具有Ig和ITIM结构域的T细胞免疫受体(TIGIT)、T细胞免疫球蛋白和粘蛋白结构域3(Tim-3)、淋巴细胞激活基因-3(LAG-3)、T细胞激活V结构域Ig抑制因子和杀伤免疫球蛋白样受体在内的五种抑制分子以及双特异性T细胞抗体(BsAbs)与MM相关的机制。此外,我们总结了这些检查点在癌症中的潜在生物学特性及其在MM通路中迅速显现的作用,并介绍了近期的相关临床试验情况。

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