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- Title
Hurdles to breakthrough in CAR T cell therapy of solid tumors.
- Authors
Marofi, Faroogh; Achmad, Harun; Bokov, Dmitry; Abdelbasset, Walid Kamal; Alsadoon, Zeid; Chupradit, Supat; Suksatan, Wanich; Shariatzadeh, Siavash; Hasanpoor, Zahra; Yazdanifar, Mahboubeh; Shomali, Navid; Khiavi, Farhad Motavalli
- Abstract
Autologous T cells genetically engineered to express chimeric antigen receptor (CAR) have shown promising outcomes and emerged as a new curative option for hematological malignancy, especially malignant neoplasm of B cells. Notably, when T cells are transduced with CAR constructs, composed of the antigen recognition domain of monoclonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner. Despite its beneficial effect, the current CAR T cell therapy approach faces myriad challenges in solid tumors, including immunosuppressive tumor microenvironment (TME), tumor antigen heterogeneity, stromal impediment, and tumor accessibility, as well as tribulations such as on-target/off-tumor toxicity and cytokine release syndrome (CRS). Herein, we highlight the complications that hamper the effectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.
- Subjects
CHIMERIC antigen receptors; T cells; T cell receptors; CYTOTOXIC T cells; CYTOKINE release syndrome; MAJOR histocompatibility complex; TUMOR antigens; IMMUNE recognition
- Publication
Stem Cell Research & Therapy, 2022, Vol 13, Issue 1, p1
- ISSN
1757-6512
- Publication type
Article
- DOI
10.1186/s13287-022-02819-x