Next-generation CAR T cells to overcome current drawbacks

• Published in: International journal of hematology 2021-11, Vol.114 (5), p.532-543
• Main Authors: Lundh, Stefan, Maji, Sayantan, Melenhorst, J. Joseph
• Format: Article
• Language: English
• Subjects: Adoptive transfer; Adverse events; Animals; Antigens; Blood diseases; Cancer; Cellular manufacture; Chimeric antigen receptors; Clinical trials; Combined Modality Therapy; Cytokines; Disease Management; Disease Susceptibility; Genetic modification; Health services; Hematological diseases; Hematology; Humans; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - economics; Immunotherapy, Adoptive - methods; Immunotherapy, Adoptive - trends; Lymphocytes; Lymphocytes T; Malignancy; Medicine; Medicine & Public Health; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - therapy; Neurotoxicity; Oncology; Patients; Prognosis; Progress in Hematology; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Receptors, Chimeric Antigen - immunology; Receptors, Chimeric Antigen - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Treatment Outcome
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-020-02923-9

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.