@article{MaucherSrourDanhofetal.2021, author = {Maucher, Marius and Srour, Micha and Danhof, Sophia and Einsele, Hermann and Hudecek, Michael and Yakoub-Agha, Ibrahim}, title = {Current limitations and perspectives of chimeric antigen receptor-T-cells in acute myeloid leukemia}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {24}, issn = {2072-6694}, doi = {10.3390/cancers13246157}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252180}, year = {2021}, abstract = {Adoptive transfer of gene-engineered chimeric antigen receptor (CAR)-T-cells has emerged as a powerful immunotherapy for combating hematologic cancers. Several target antigens that are prevalently expressed on AML cells have undergone evaluation in preclinical CAR-T-cell testing. Attributes of an 'ideal' target antigen for CAR-T-cell therapy in AML include high-level expression on leukemic blasts and leukemic stem cells (LSCs), and absence on healthy tissues, normal hematopoietic stem and progenitor cells (HSPCs). In contrast to other blood cancer types, where CAR-T therapies are being similarly studied, only a rather small number of AML patients has received CAR-T-cell treatment in clinical trials, resulting in limited clinical experience for this therapeutic approach in AML. For curative AML treatment, abrogation of bulk blasts and LSCs is mandatory with the need for hematopoietic recovery after CAR-T administration. Herein, we provide a critical review of the current pipeline of candidate target antigens and corresponding CAR-T-cell products in AML, assess challenges for clinical translation and implementation in routine clinical practice, as well as perspectives for overcoming them.}, language = {en} } @article{ZhouRascheKortuemetal.2020, author = {Zhou, Xiang and Rasche, Leo and Kort{\"u}m, K. Martin and Danhof, Sophia and Hudecek, Michael and Einsele, Hermann}, title = {Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.620312}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219911}, year = {2020}, abstract = {In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their "last chance" and a "hope of cure". However, severe adverse events (AEs) and even toxic death related to CAR T cell therapy have been observed. The management of AEs related to CAR T cell therapy represents a new challenge, as the pathophysiology is not fully understood and there is still no well-established standard of management. With regard to CAR T cell associated toxicities in MM, in this review, we will provide an overview of experience from clinical trials, pathophysiology, and management strategies.}, language = {en} }