Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism

Stem Cell Research & Therapy

Rebar N. Mohammed¹  Faroogh Marofi²  Navid Shomali³  Safa Tahmasebi⁴  Heshu Sulaiman Rahman⁵  Alexei Valerievich Yumashev⁶  Farhad Motavalli Khiavi⁷  Max Stanley Chartrand⁸  Denis Kaigorodov⁹  Yashwant Pathak^1,10  Roza Motavalli^1,11  Mostafa Jarahian^1,12  Alexander Markov^1,13 

[1] Bone Marrow Transplant Center, Hiwa Cancer Hospital, Suleimanyah, Iraq;Department of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;Department of Immunology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran;Department of Physiology, College of Medicine, University of Suleimanyah, Sulaymaniyah, Iraq;Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Trubetskaya St., 8-2, 119991, Moscow, Russian Federation;Department of Virology, Pasteur Institute of Iran, Tehran, Iran;DigiCare Behavioral Research, Casa Grande, AZ, USA;Director of Research Institute “MitoKey”, Moscow State Medical University, Moscow, Russian Federation;Faculty Affairs, Taneja College of Pharmacy, University of South Florida, Tampa, FL, USA;Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia;Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;Toxicology and Chemotherapy Unit (G401), German Cancer Research Center, 69120, Heidelberg, Germany;Tyumen State Medical University, Tyumen Industrial University, Tyumen, Russian Federation;

关键词: Multiple myeloma;    Adoptive cell therapy;    CAR-T cells;    Hematological malignancy;   

DOI  :  10.1186/s13287-021-02283-z

来源: Springer

【 摘 要 】

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell’s history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells.

【 授权许可】

CC BY