Chimeric Antigen Receptor-Engineered T-Cells - A New Way and Era for Lymphoma Treatment

Author(s): Romeo G. Mihăilă*

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 14 , Issue 4 , 2019

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Background: Patients with refractory or relapsed diffuse large B-cell lymphoma have a poor prognosis with the current standard of care.

Objective: Chimeric Antigen Receptor T-cells (CAR T-cells) are functionally reprogrammed lymphocytes, which are able to recognize and kill tumor cells. The aim of this study is to make progress in this area.

Methods: A mini-review was achieved using the articles published in Web of Science and PubMed in the last year and the new patents were made in this field.

Results: The responses to CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel are promising; the objective response rate can reach up to 83%, and the complete response rate ranges between 40 and 58%. About half of the patients may have serious side effects, such as cytokine release syndrome and neurotoxicity. Current and future developments include the improvement of CAR T-cell expansion and polyfunctionality, the combined use of CAR T-cells with a fusion protein between interferon and an anti-CD20 monoclonal antibody, with checkpoint inhibitors or small molecule sensitizers that have apoptotic-regulatory effects. Furthermore, the use of IL-12-expressing CAR T-cells, an improved technology for the production of CAR T-cells based on targeted nucleases, the widespread use of allogeneic CAR T-cells or universal CAR T-cells obtained from genetically engineered healthy donor T-cells are future developments actively considered.

Conclusion: CAR T-cell therapy significantly improved the outcome of patients with relapsed or refractory diffuse large B-cell lymphoma. The advances in CAR T-cells production technology will improve the results and enable the expansion of this new immunotherapy.

Keywords: Axicabtagene ciloleucel, chimeric antigen receptor, cytokine release syndrome, diffuse large B-cell lymphoma, tisagenlecleucel, tocilizumab.

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Year: 2019
Page: [312 - 323]
Pages: 12
DOI: 10.2174/1574892814666191022164641
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