Atanackovic Djordje, Radhakrishnan Sabarinath V, Bhardwaj Neelam, Luetkens Tim
Multiple Myeloma Program, Hematology and Hematologic Malignancies, University of Utah/Huntsman Cancer Institute, Salt Lake City, UT, USA.
Br J Haematol. 2016 Mar;172(5):685-98. doi: 10.1111/bjh.13889. Epub 2016 Jan 20.
The introduction of chimeric antigen receptor (CAR)-modified T cells has revolutionized immunotherapy and cancer treatment as a whole. However, so far, clinical efficacy has only been demonstrated for CD19-positive B cell lymphomas. For Multiple Myeloma (MM), the second most common haematological malignancy, there are currently no clinical results supporting the usefulness of the adoptive transfer of CAR-modified T cells. This might be related to the fact that an ideal surface target has not yet been identified or the presence of strong local immunosuppression in the tumour microenvironment, which is a hallmark of MM. In this review, we provide a comprehensive overview of promising target molecules for CAR T cell approaches in MM and we outline a number of ways in which the local immunosuppression in MM can be overcome. By providing a strategy for the design of CAR T cell treatments for MM we hope to transform this new therapeutic approach into a valuable tool within the therapeutic armamentarium for MM.
嵌合抗原受体(CAR)修饰的T细胞的引入彻底改变了免疫疗法及整个癌症治疗领域。然而,迄今为止,临床疗效仅在CD19阳性B细胞淋巴瘤中得到证实。对于第二常见的血液系统恶性肿瘤多发性骨髓瘤(MM),目前尚无临床结果支持CAR修饰的T细胞过继性转移的有效性。这可能与尚未确定理想的表面靶点这一事实有关,也可能与肿瘤微环境中存在强大的局部免疫抑制有关,而这是MM的一个特征。在本综述中,我们全面概述了MM中CAR-T细胞疗法有前景的靶分子,并概述了多种可克服MM局部免疫抑制的方法。通过提供MM的CAR-T细胞治疗设计策略,我们希望将这种新的治疗方法转变为MM治疗武器库中的一种有价值的工具。