Journal
INTERNATIONAL JOURNAL OF HEMATOLOGY
Volume 114, Issue 5, Pages 532-543Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s12185-020-02923-9
Keywords
Chimeric antigen receptor; CAR T cell; Cancer; Immunotherapy
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CAR T-cell therapy, as a rapidly emerging treatment option in oncology, has shown significant efficacy and potential for cure in certain relapsed/refractory patients with hematologic malignancy. However, there are various barriers for widespread adoption of CAR T therapy, including cellular manufacturing limitations, adverse events post-infusion, and host rejection of non-human CARs. Future clinical trials need to address unique mechanisms of relapse in different hematologic diseases to enhance the efficacy of CAR T treatment.
As a rapidly emerging treatment in the oncology field, adoptive transfer of autologous, genetically modified chimeric antigen receptor (CAR) T cells has shown striking efficacy and is curative in certain relapsed/refractory patients with hematologic malignancy. This treatment modality of using a living drug offers many tantalizing and novel therapeutic strategies for cancer patients whose remaining treatment options may have otherwise been limited. Despite the early success of CAR T cells in hematologic malignancies, many barriers remain for widespread adoption. General barriers include cellular manufacturing limitations, baseline quality of the T cells, adverse events post-infusion such as cytokine release syndrome (CRS) and neurotoxicity, and host rejection of non-human CARs. Additionally, each hematologic disease presents unique mechanisms of relapse which have to be addressed in future clinical trials if we are to augment the efficacy of CAR T treatment. In this review, we will describe current barriers to hindering efficacy of CAR T-cell treatment for hematologic malignancies in a disease-specific manner and review recent innovations aimed at enhancing the potency and applicability of CAR T cells, with the overall goal of building a framework to begin incorporating this form of therapy into the standard medical management of blood cancers.
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