RETRACTED ARTICLE: Hurdles to breakthrough in CAR T cell therapy of solid tumors
Faroogh Marofi, Harun Achmad, Dmitry Olegovich Bokov, Walid Kamal Abdelbasset, Zeid Alsadoon, Supat Chupradit, Wanich Suksatan, Siavash Shariatzadeh, Zahra Hasanpoor, Mahboubeh Yazdanifar, Navid Shomali, Farhad Motavalli Khiavi
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.