Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients

Stem Cell Research & Therapy

Heshu Sulaiman Rahman¹  Walid Kamal Abdelbasset²  Safa Tahmasebi³  Zaid Mahdi Jaber Al-Obaidi⁴  Max Stanley Chartrand⁵  Abduladheem Turki Jalil⁶  Wanich Suksatan⁷  Mostafa Jarahian⁸  Ali Hassanzadeh⁹  Faroogh Marofi⁹  Hossein Saeedi⁹  Behzad Baradaran⁹  Navid Shomali⁹  Aleksei Evgenievich Dorofeev^1,10  Majid Ahmadi^1,11  Yashwant Pathak^1,12 

[1] College of Medicine, University of Sulaimani, Sulaimaniyah, Iraq;Department of Medical Laboratory Sciences, Komar University of Science and Technology, Chaq-Chaq Qularaise, Sulaimaniyah, Iraq;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;Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;Department of Pharmaceutical Chemistry, College of Pharmacy, University of Alkafeel, 54001, Najaf, Iraq;Department of Chemistry and Biochemistry, College of Medicine, University of Kerbala, 56001, Karbala, Iraq;DigiCare Behavioral Research, Casa Grande, AZ, USA;Faculty of Biology and Ecology, Yanka Kupala State University of Grodno, Grodno, Belarus;Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, 10210, Bangkok, Thailand;German Cancer Research Center, Toxicology and Chemotherapy, No. 2, Floor 4 Unit (G401), 69120, Heidelberg, Germany;Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;Sechenov First Moscow State Medical University, Moscow, Russia;Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;Taneja College of Pharmacy, University of South Florida, Tampa, FL, USA;Department of Pharmaceutics, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia;

关键词: Acute myeloid leukemia;    Adoptive cell therapy;    Chimeric antigen receptor T cells;    Hematological malignancy;    Target antigen;   

DOI  :  10.1186/s13287-021-02420-8

来源: Springer

【 摘 要 】

Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.

【 授权许可】

CC BY