Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies

被引:4
作者
Olejarz, Wioletta [1 ,2 ]
Sadowski, Karol [1 ,2 ,3 ]
Szulczyk, Daniel [4 ]
Basak, Grzegorz [3 ]
机构
[1] Med Univ Warsaw, Fac Pharm, Dept Biochem & Pharmacogen, PL-02097 Warsaw, Poland
[2] Med Univ Warsaw, Ctr Preclin Res, PL-02097 Warsaw, Poland
[3] Med Univ Warsaw, Dept Hematol Transplantat & Internal Med, PL-02097 Warsaw, Poland
[4] Med Univ Warsaw, Chair & Dept Biochem, PL-02097 Warsaw, Poland
关键词
CAR-T; EVs; immunotherapy; biomarkers; hematological malignancies; checkpoint inhibitors; TME; ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; EPSTEIN-BARR-VIRUS; CELL-FREE DNA; CIRCULATING TUMOR DNA; NON-HODGKIN-LYMPHOMA; INHIBITORY RECEPTORS; IMMUNE MICROENVIRONMENT; GENE REARRANGEMENTS; MULTIPLE-MYELOMA;
D O I
10.3390/ijms25147743
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chimeric antigen receptor T-cell (CAR-T) therapy is a novel anticancer therapy using autologous or allogeneic T-cells. To date, six CAR-T therapies for specific B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma (MM) have been approved by the Food and Drug Administration (FDA). Significant barriers to the effectiveness of CAR-T therapy include cytokine release syndrome (CRS), neurotoxicity in the case of Allogeneic Stem Cell Transplantation (Allo-SCT) graft-versus-host-disease (GVHD), antigen escape, modest antitumor activity, restricted trafficking, limited persistence, the immunosuppressive microenvironment, and senescence and exhaustion of CAR-Ts. Furthermore, cancer drug resistance remains a major problem in clinical practice. CAR-T therapy, in combination with checkpoint blockades and bispecific T-cell engagers (BiTEs) or other drugs, appears to be an appealing anticancer strategy. Many of these agents have shown impressive results, combining efficacy with tolerability. Biomarkers like extracellular vesicles (EVs), cell-free DNA (cfDNA), circulating tumor (ctDNA) and miRNAs may play an important role in toxicity, relapse assessment, and efficacy prediction, and can be implicated in clinical applications of CAR-T therapy and in establishing safe and efficacious personalized medicine. However, further research is required to fully comprehend the particular side effects of immunomodulation, to ascertain the best order and combination of this medication with conventional chemotherapy and targeted therapies, and to find reliable predictive biomarkers.
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页数:23
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