Bispecific T-cell engager antibodies (BiTE) have been explored as a means to recruit cytolytic T cells to kill tumor cells. The transferrin receptor (TfR) is highly expressed on the surface of rapidly proliferating tumor cells. Therefore, it holds great potential in T cell redirecting therapies. In this paper, we developed a BiTE targeting TfR and CD3 (TfR-BiTE) and studied its therapeutic impact on TfR-positive cancer. TfR-BiTE had the ability to induce the selective lysis of various TfR-positive cancer cells through the activation of T cells, the release of cytokines, and then the coming proliferation of T cells, whereas TfR-negative cells were not affected. In a subcutaneous HepG2 xenograft model, low concentrations of TfR-BiTE inhibited tumor growth. Taken together, these results reveal that TfR-BiTE can selectively deplete TfR-positive HepG2 cells; hence, it represents a novel immunotherapeutic approach for the treatment of hepatocellular carcinoma.
Here we introduce an enzyme-free and colorimetric detection strategy for adenosine. The approach is based on that the adenosine triggers catalyzed hairpin assembly, which induces gold nanoparticles aggregation via crosslinking.
Introduction Fibroblast activation protein (FAP) overexpression on cancer-associated fibroblasts (CAFs) is associated with poor prognosis and worse clinical outcomes. Selective ablation of pro-tumorgenic FAP + stromal cells with CAR-T cells may be a new therapeutic strategy. However, the clinical use of FAP-CAR T cells is suggested to proceed with caution for occasional poor efficacy and induction of on-target off-tumor toxicity (OTOT), including lethal osteotoxicity and cachexia. Hence, more investigations and preclinical trials are required to optimize the FAP-CAR T cells and to approve their safety and efficacy. Methods In this study, we designed second-generation CAR T cells targeting FAP with 4-1BB as a co-stimulatory molecule, and tested their cytotoxicity against FAP-positive cells (hFAP-HT1080 cells and a variety of primary CAFs) in vitro and in Cell line-derived xenograft (CDX) and a patient-derived xenograft (PDX) model. Results Results showed that our FAP-CAR T cells were powerfully potent in killing human and murine FAP-positive tumor cells and CAFs in multiple types of tumors in BALB/c and C57BL/6 mice and in patient-derived xenografts (PDX) model. And they were proved to be biologically safe and exhibit low-level OTOT. Discussion Taken together, the human/murine cross-reactive FAP-CAR T cells were powerfully potent in killing human and murine FAP positive tumor cells and CAFs. They were biologically safe and exhibit low-level OTOT, warranting further clinical investigation into our FAP-CAR T cells.
Abstract In the present study, we here report a case of 71-year-old woman, with bone destruction of L5 vertebral body showing lower of SUVmax for FAPI compared to FDG PET/CT imaging. To our knowledge, this present case is the first study to reveal that 68Ga-FAPI had lower tumour-to-background ratio in detecting bone metastasis from PTCMCa-FV.
Objective To evaluate the efficacy 18 F-FDG PET/CT in diagnosis and prognosis for nasopharyngeal carcinoma(NPC) patients during follow-up after comprehensive therapy.Methods A total of 89NPC patients after comprehensive therapy were included,and the diagnostic results of 18 F-FDG PET/CT and traditional imaging were analyzed and compared with histopathological diagnosis or clinical follow-up data retrospectively.The diagnostic sensitivity,specificity,accuracy rate,positive predictive value(PPV) and negative predictive value(NPV) of residual,recurrent or metastasis were calculated,respectively.The qualitative diagnosis using the maximal standard uptake value(SUV max) was determined.ROC curves were determined to assess the optimal cutoff value for evaluating diagnostic value of 18 F-FDG PET/CT and predicting survival,while qualitative diagnosis was predicted survival.COX proportional hazards regression model analysis was performed to identify the prognostic factors which impact overall survival(OS) and disease-free survival(DFS).Results In all 89patients,five-year OS of all patients was 73.00%,and the mean survival time was(69.22±4.46) months.The diagnostic sensitivity,specificity,accuracy rate,PPV and NPV of 18 F-FDG PET/CT and conventional imaging was 100%(59/59),90.20%(46/51),95.45%(105/110),92.19%(59/64),100%(46/46) and 75.86%(44/58),78.85%(41/52),77.27%(85/110),80.00%(44/55),72.73%(40/55),respectively.The sensitivity and accuracy rate of 18 F-FDG PET/CT were high than those of traditional imaging(both P0.01).From ROC curve,the cut off value of SUV max was 2.5,which might be the best diagnostic value in the follow-up of NPC.Patients with SUVmaxbelow 2.5had significantly better 5-year OS than those with SUV max ≥ 2.5(81.90% vs 62.00%,P=0.036).18 F-FDG PET negative patients had long 5-year OS than positive ones(59.90% vs 100%,P=0.006).COX proportional hazards regression model analysis showed both SUV max(relative risk [ RR ] =1.205,P=0.014) and number of lesions(RR=2.734,P=0.005) could be used to predict OS.For DFS,number of lesions(RR=2.105,P=0.008) might have predictive relevance.Conclusion 18 F-FDG PET/CT imaging has significantly higher sensitivity and accuracy rate than conventional imaging in detection of the residual,recurrent and metastasis of NPC after comprehensive therapy.SUV max being 2.5may be a relatively good diagnostic value in the following-up,and may also have great valuable for predicting long-term survival.SUVmaxand number of lesions may be predictors for OS and DFS,and number of lesions may be an important factor for DFS.
Multiple myeloma (MM) is a hematological malignancy of plasma cell origin. Cardiac amyloidosis (CA) is a common form of heart damage caused by MM and is associated with a poor prognosis. This study was a prospective cohort study and was aimed at evaluating the clinical predictive value of extracellular volume fraction (ECV) based on cardiovascular magnetic resonance (CMR) T1 mapping for cardiac amyloidosis and cardiac dysfunction in MM patients. Fifty-one newly diagnosed MM patients in Zhongnan Hospital of Wuhan University were enrolled in the study. A total of 19 patients (19/51; 37.25%) developed CA. The basal ECV of CA group was significantly higher than that of the non-CA group (p < 0.01). Multivariate logistic regression analysis showed that basal ECV (OR = 1.551, 95% CI 1.084-2.219, p < 0.05) and LDH1 level (OR = 1.150, 95% CI 1.010-1.310, p < 0.05) were two independent risk factors for CA. Further study demonstrated that basal ECV in the heart failure group was significantly higher than that of the nonheart failure group (p < 0.01). Notably, ROC curve showed that basal ECV had a good predictive value for CA and heart failure, with AUC of 0.911 and 0.893 (all p < 0.01), and the best cutoff values of 38.35 and 37.45, respectively. Taken together, basal ECV is a good predictor of CA and heart failure for MM patients.
Abstract The 78-kDa glucose-regulated protein (GRP78) has extracellular, anti-inflammatory properties that can aid resolving inflammation. It has been established previously that GRP78 induced myeloid CD11c+ cell differentiation into distinct tolerogenic cells. This tolerance induction makes GRP78 a potential therapeutic agent for transplanted allogeneic grafts and autoimmune diseases, such as type 1 diabetes. In this research, it is revealed that rmGRP78-treated NOD mice bone marrow-derived CD11c+ cells (GRP78-DCs) highly expressed B7-H4 but down-regulated CD86 and CD40, and retained a tolerogenic signature even after stimulation by LPS. In the assessment of in vivo therapeutic efficacy after the adoptive transfer of GRP78-DCs into NOD mice, fluorescent imaging analyses revealed that the transfer specifically homed in inflamed pancreases, promoting β-cell survival and alleviating insulitis in NOD mice. The adoptive transfer of GRP78-DCs also helped reduce Th1, Th17, and CTL, suppressing inflammatory cytokine production in vivo. The findings suggest that adoptive GRP78-DC transfer is critical to resolving inflammation in NOD mice and may have relevance in a clinical setting.
1035 Objectives: Our study intended to explore the association combining 18F-FDG PET/CT metabolic parameters and clinical features and lymphovascular invasion status in non-small-cell lung cancer (NSCLC). Methods: This retrospective study included 161 patients (median age, 63 years; interquartile range, 55.5 - 67.0 years) from January 2018 to November 2020 with NSCLC who underwent 18F-FDG PET/CT scan within one month before surgery in our hospital. The PET/CT metabolic parameters including maximum and mean standard uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary lesion were measured. The associations between PET/CT parameters and clinical characteristics (age, sex, smoking, serum tumor marker, histological type, T-stage, N-stage, TNM stage, pleural invasion) and lymphovascular invasion status were analyzed. Multivariate logistic regression analysis was performed to explore independent predictive factors for lymphovascular invasion. Results: A total of 161 eligible patients with NSCLC enrolled in this study, including 111 males and 50 females, were divided into two groups, lymphovascular invasion-positive group (n=38, 23.6%) and lymphovascular invasion-negative group (n=123, 76.4%). Histopathological findings included adenocarcinoma (n=119), squamous cell carcinoma (n=38), undefined NSCLC (n=1) and adenosquamous carcinoma (n=3). The average of SUVmax and SUVmean of primary lesion were 15.43 ± 5.91 vs. 11.73 ± 7.53 (p = 0.006) and 6.02 ± 1.58 vs. 5.07 ± 2.03 (p = 0.009), in the lymphovascular invasion-positive group and lymphovascular group-negative group, respectively. The median MTV and TLG were 15.80 (8.22, 31.07) vs. 5.47 (1.47, 20.17) (p
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