Dataset Information

Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients.

ABSTRACT: Soft tissue sarcomas (STSs) are heterogeneous and aggressive malignancies with few effective therapies available. We have developed T cells expressing a vascular endothelial growth factor receptor 2 (VEGFR2)-specific chimeric antigen receptor (CAR) to establish a tumor angiogenesis-specific CAR-T cells impacting cancers (TACTICs) therapy. In this study, we optimized the manufacturing and transportation of mRNA-transfected anti-VEGFR2 CAR-T cells and collected information that allowed the extrapolation of the efficacy and safety potential of TACTICs therapy for STS patients. Although 5-methoxyuridines versus uridines did not improve CAR-mRNA stability in T cells, the utilization of CleanCap as a 5' cap-structure extended the CAR expression level, increasing VEGFR2-specific cytotoxicity. Furthermore, 4 °C preservation conditions did not affect the viability/cytotoxicity of CAR-T cells, contrarily to a freeze-thaw approach. Importantly, immunohistochemistry showed that most of the STS patients' specimens expressed VEGFR2, suggesting a great potential of our TACTICs approach. However, VEGFR2 expression was also detected in normal tissues, stressing the importance of the application of a strict monitoring schedule to detect (and respond to) the occurrence of adverse effects in clinics. Overall, our results support the development of a "first in humans" study to evaluate the potential of our TACTICs therapy as a new treatment option for STSs.

SUBMITTER: Fujiwara K

PROVIDER: S-EPMC7598286 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients.

Fujiwara Kento K Sasawatari Shigemi S Nakai Sho S Imaeda Keisuke K Nagai Seina S Matsuno Yoshihiro Y Hatanaka Kanako K Hatanaka Yutaka Y Takenaka Satoshi S Okada Naoki N

Cancers 20200923 10

Soft tissue sarcomas (STSs) are heterogeneous and aggressive malignancies with few effective therapies available. We have developed T cells expressing a vascular endothelial growth factor receptor 2 (VEGFR2)-specific chimeric antigen receptor (CAR) to establish a tumor angiogenesis-specific CAR-T cells impacting cancers (TACTICs) therapy. In this study, we optimized the manufacturing and transportation of mRNA-transfected anti-VEGFR2 CAR-T cells and collected information that allowed the extrapo ...[more]

PMID: 32977646

Similar Datasets

Project description:The preoperative C-reactive protein/Albumin ratio (CAR) is valuable for predicting the prognosis of patients with various types of cancers. The aim of the present study is to investigate the prognostic value of the preoperative CAR and compare it with other systemic inflammatory response markers in patients with soft tissue sarcoma (STS).This retrospective study included 206 patients with STS. The optimal cutoff value of the CAR was determined by receiver operating characteristic (ROC) analysis. The impact of the CAR and other clinicopathological features on overall survival (OS) and disease-free survival (DFS) was evaluated using univariate and multivariate Cox regression analyses. Kaplan-Meier survival analyses were used to compare groups classified by the CAR. Additionally, the area under the receiver operating characteristic curve (AUC) was used to compare the predictive ability of the CAR, high-sensitivity modified Glasgow prognostic score (Hs-mGPS), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR).The optimal cut-off value of the CAR was 0.1035 according to the ROC analysis. An increased CAR (?0.1035) was significantly associated with older age, larger tumor size, deep tumor location, higher tumor grade and more advanced American Joint Committee on Cancer (AJCC) stage (all P<0.05). Patients with an elevated CAR (?0.1035) exhibited a shorter median survival time and lower 5-year OS rate than those with a CAR<0.1035 (68.2 vs 115.8 months, P = 0.000; 44.6% vs 80.9%, P = 0.000, respectively). The results of a multivariate analysis indicated that the CAR (Hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.47-4.14, P = 0.001) was an independent prognostic factor for OS along with tumor grade (P<0.05). Additionally, the CAR exhibited a greater AUC value (0.662) than the NLR and PLR, but the value was equal to the Hs-mGPS.The preoperative CAR is an independent prognostic factor predicting prognosis in STS and exhibits superior prognostic ability compared to the established inflammation-based prognostic indices.

Dataset Information

Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients.

Publications

Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets