Hurdles to breakthrough in CAR T cell therapy of solid tumors.

Faroogh Marofi, Harun Achmad, Dmitry Bokov, Walid Kamal Abdelbasset, Zeid Alsadoon, Supat Chupradit, Wanich Suksatan, Siavash Shariatzadeh, Zahra Hasanpoor, Mahboubeh Yazdanifar, Navid Shomali, Farhad Motavalli Khiavi

Journal: Stem cell research & therapy 2022;13(1):140

PMID: 35365241

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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.

Address: Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Pediatric Dentistry, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia.; Institute of Pharmacy, Sechenov First Moscow State Medical University, 8 Trubetskaya St., bldg. 2, Moscow, 119991, Russian Federation.; Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr., Moscow, 109240, Russian Federation.; Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia.; Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt.; Dentistry Department, College of Technical Engineering, The Islamic University, Najaf, Iraq.; Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.; Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, 10210, Thailand.; Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.; Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.; Department of Virology, Pasteur Institute of Iran, Tehran, Iran. [email protected].

DOI: 10.1186/s13287-022-02819-x

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https://medlineplus.gov/cancer.html

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https://antibodies.cancer.gov/detail/CPTC-HLA-C-1

MeSH Terms: Humans, Immunotherapy, Adoptive, Neoplasms, Receptors, Chimeric Antigen, T-Lymphocytes, Tumor Microenvironment