Ackley James, Ochoa Miguel Armenta, Ghoshal Delta, Roy Krishnendu, Lonial Sagar, Boise Lawrence H
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA.
The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Cancers (Basel). 2021 Sep 24;13(19):4787. doi: 10.3390/cancers13194787.
Multiple myeloma is an incurable disease of malignant plasma cells and an ideal target for modern immune therapy. The unique plasma cell biology maintained in multiple myeloma, coupled with its hematological nature and unique bone marrow microenvironment, provide an opportunity to design specifically targeted immunotherapies that selectively kill transformed cells with limited on-target off-tumor effects. Broadly defined, immune therapy is the utilization of the immune system and immune agents to treat a disease. In the context of multiple myeloma, immune therapy can be subdivided into four main categories: immune modulatory imide drugs, targeted antibodies, adoptive cell transfer therapies, and vaccines. In recent years, advances in all four of these categories have led to improved therapies with enhanced antitumor activity and specificity. In IMiDs, modified chemical structures have been developed that improve drug potency while reducing dose limiting side effects. Targeted antibody therapies have resulted from the development of new selectively expressed targets as well as the development of antibody drug conjugates and bispecific antibodies. Adoptive cell therapies, particularly CAR-T therapies, have been enhanced through improvements in the manufacturing process, as well as through the development of CAR constructs that enhance CAR-T activation and provide protection from a suppressive immune microenvironment. This review will first cover in-class breakthrough therapies for each of these categories, as well as therapies currently utilized in the clinic. Additionally, this review will explore up and coming therapeutics in the preclinical and clinical trial stage.
多发性骨髓瘤是一种无法治愈的恶性浆细胞疾病，是现代免疫治疗的理想靶点。多发性骨髓瘤中维持的独特浆细胞生物学特性，及其血液学性质和独特的骨髓微环境，为设计特异性靶向免疫疗法提供了机会，这种疗法能选择性地杀死转化细胞，同时将脱靶的肿瘤外效应限制在最低限度。广义而言，免疫治疗是利用免疫系统和免疫制剂来治疗疾病。在多发性骨髓瘤的背景下，免疫治疗可细分为四大类：免疫调节性酰亚胺药物、靶向抗体、过继性细胞转移疗法和疫苗。近年来，这四类疗法均取得了进展，带来了抗肿瘤活性和特异性增强的改良疗法。在免疫调节性酰亚胺药物方面，已开发出改良的化学结构，提高了药物效力，同时降低了剂量限制性副作用。靶向抗体疗法得益于新的选择性表达靶点的开发，以及抗体药物偶联物和双特异性抗体的开发。过继性细胞疗法，尤其是嵌合抗原受体T细胞（CAR-T）疗法，通过改进制造工艺以及开发增强CAR-T激活并提供免受抑制性免疫微环境影响的CAR构建体而得到了改进。本综述将首先介绍这些类别中的各类突破性疗法，以及目前在临床上使用的疗法。此外，本综述还将探讨处于临床前和临床试验阶段的新兴疗法。
