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

Marofi, Faroogh; Tahmasebi, Safa; Rahman, Heshu Sulaiman; Kaigorodov, Denis; Марков, А. В.; Yumashev, Alexei Valerievich; Shomali, Navid; Chartrand, Max Stanley; Pathak, Yashwant; Mohammed, Rebar N.; Jarahian, Mostafa; Motavalli, Roza; Khiavi, Farhad Motavalli

doi:10.1186/s13287-021-02283-z

Cited by 21 publications

(18 citation statements)

References 185 publications

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“…CARs are designed by using part of mAbs and can recognize only one specific antigen epitope. Therefore, CAR T cell engineering is implemented first by isolation of patients’ T cells, next by incorporating the CARs into the T cells, expansion of newly generated CAR T cells, and then re-infusion of newly engineered cells into the patient’s body [ 59 , 60 ].…”

Section: Car T Cell Therapymentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Car T Cell Therapymentioning

confidence: 99%

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

et al. 2021

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“…The engineering of autologous peripheral blood (PB) T lymphocytes to selectively identify tumor-associated antigens (TAAs) on the tumor cell surface is currently a well-established method [ 33 ]. The ability of T cell receptor (TCR) and CAR therapies by well-established engineering methods is greatly exemplified by the stimulating clinical outcomes achieved with CTA New York esophageal squamous cell carcinoma-1 (NY-ESO-1) TCR and CD19-specific CAR T cells [ 34 , 35 ].…”

Section: Car Redirected Cells Manufacturementioning

confidence: 99%

Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress

et al. 2022

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Due to the overexpression or amplification of human epidermal growth factor receptor 2 (HER2) with poor prognosis in a myriad of human tumors, recent studies have focused on HER2-targeted therapies. Deregulation in HER2 signaling pathways is accompanied by sustained tumor cells growth concomitant with their migration and also tumor angiogenesis and metastasis by stimulation of proliferation of a network of blood vessels. A large number of studies have provided clear evidence that the emerging HER2-directed treatments could be the outcome of patients suffering from HER2 positive breast and also gastric/gastroesophageal cancers. Thanks to its great anti-tumor competence, immunotherapy using HER2-specific chimeric antigen receptor (CAR) expressing immune cell has recently attracted increasing attention. Human T cells and also natural killer (NK) cells can largely be found in the tumor microenvironment, mainly contributing to the tumor immune surveillance. Such properties make them perfect candidate for genetically modification to express constructed CARs. Herein, we will describe the potential targets of the HER2 signaling in tumor cells to clarify HER2-mediated tumorigenesis and also discuss recent findings respecting the HER2-specific CAR-expressing immune cells (CAR T and CAR NK cell) for the treatment of HER2-expressing tumors.

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“…Additionally, CD19 CAR T cell therapy is showing promise in other hematological cancers such as multiple myeloma [ 116 ]. This is remarkable because multiple myeloma entirely consists of plasma cells which are CD19 negative.…”

Section: Adoptive T Cell Transfer Therapy—a Focus On Car T Cellsmentioning

confidence: 99%

T Cell Engaging Immunotherapies, Highlighting Chimeric Antigen Receptor (CAR) T Cell Therapy

Bousser

Callewaert

Festjens

2021

Cancers

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In the past decade, chimeric antigen receptor (CAR) T cell technology has revolutionized cancer immunotherapy. This strategy uses synthetic CARs to redirect the patient’s own immune cells to recognize specific antigens expressed on the surface of tumor cells. The unprecedented success of anti-CD19 CAR T cell therapy against B cell malignancies has resulted in its approval by the US Food and Drug Administration (FDA) in 2017. However, major scientific challenges still remain to be addressed for the broad use of CAR T cell therapy. These include severe toxicities, limited efficacy against solid tumors, and immune suppression in the hostile tumor microenvironment. Furthermore, CAR T cell therapy is a personalized medicine of which the production is time- and resource-intensive, which makes it very expensive. All these factors drive new innovations to engineer more powerful CAR T cells with improved antitumor activity, which are reviewed in this manuscript.

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

Cited by 21 publications

References 185 publications

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

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

Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress

T Cell Engaging Immunotherapies, Highlighting Chimeric Antigen Receptor (CAR) T Cell Therapy

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