CAR-T Cells in the Treatment of Ovarian Cancer: A Promising Cell Therapy

Abstract

Ovarian cancer (OC) is among the most common gynecologic malignancies with a poor prognosis and a high mortality rate. Most patients are diagnosed at an advanced stage (stage III or IV), with 5-year survival rates ranging from 25% to 47% worldwide. Surgical resection and first-line chemotherapy are the main treatment modalities for OC. However, patients usually relapse within a few years of initial treatment due to resistance to chemotherapy. Cell-based therapies, particularly adoptive T-cell therapy and chimeric antigen receptor T (CAR-T) cell therapy, represent an alternative immunotherapy approach with great potential for hematologic malignancies. However, the use of CAR-T-cell therapy for the treatment of OC is still associated with several difficulties. In this review, we comprehensively discuss recent innovations in CAR-T-cell engineering to improve clinical efficacy, as well as strategies to overcome the limitations of CAR-T-cell therapy in OC.

Dual‑regulated oncolytic adenovirus carrying ERCC1‑siRNA gene possesses potent antitumor effect on ovarian cancer cells

“…As depicted in Fig. 3C , in the presence of DDP, cancer cells transduced with Ad-siERCC1 (74.19%) exhibited significantly lower cell viability compared with those transduced with Ad-NC (56.85%) six days post-transduction (Independent-Samples t test; t ( 6 ) =−7.420; P<0.001). Additionally, cell cycle analysis revealed that SKOV3 cells in all groups were arrested in the G 1 phase when compared with the control group (control group: 46.60%; Ad-NC: 63.79%; Ad-siERCC1: 66.05%; DDP: 68.42%; DDP + Ad-NC: 70.56%; DDP + Ad-siERCC1: 75.12%; one-way ANOVA, G 1 : F ( 5 , 12 )= 148.758, P<0.001; vs. the control group, Ad-NC: P<0.001; Ad-siERCC1: P<0.001; DDP: P<0.001; DDP + Ad-NC: P<0.001; DDP + Ad-siERCC1: P<0.001).…”

“…At MOI=10, the mRNA and protein levels of ERCC1 were validated using RT-qPCR and immunoblotting techniques, revealing a decrease in ERCC1 mRNA (~60% less than control; Independent-Samples t test; t ( 6 ) =36.842; P<0.001; Fig. 2B ) and protein (>3-fold less than control) (Independent-Samples t test; t ( 6 ) =24.036; P<0.001; Fig. 2C ) upon Ad-siERCC1 treatment.…”

“…The current front-line standard of care for ovarian cancer involves surgery followed by platinum-taxane maintenance chemotherapy ( 6 , 7 ). However, chemotherapy resistance remains a significant factor contributing to the high mortality rate in ovarian cancer ( 5 ).…”

LRP8 promotes tumorigenesis in ovarian cancer through inhibiting p53 signaling

“…OC is a type of malignant cancer that starts in the ovaries, which are part of the female reproductive system (Kossai et al, 2018). In addition to traditional treatment strategies, such as surgery, chemotherapy, and radiation therapy, immunotherapy and targeted therapy are also available for the clinical treatment of OC patients (Kurnit et al, 2021; Zhang et al, 2023). However, immunotherapies show less success in OC, and the use of immunotherapy is limited by immune profiling of OC patients, such as mismatch repair and homologous repair deficiency (Morand et al, 2021).…”

MMP-3 gene regulates the carcinogenesis and metabolic process of ovarian cancer, evidence from a Chinese population: Observational study and meta-analysis

“…Studies have reported that tumor metastasis is the main risk factor for ovarian cancer progression, and the polymorphism of genes regulating OC metastasis participates in OC pathogenesis. [ 5 , 6 ] Single nucleotide polymorphism is a common form of gene variation, with one single nucleotide polymorphism locus for every 1000 nucleotides, which has a crucial role in the tumor pathogenesis. The abnormal expression of matrix metalloproteinase-3 (MMP-3) participates in the occurrence of OC.…”