For subcellular imaging, activating probes by specific species in targeted organelles is an attractive strategy to eliminate nonspecific signals during transport. The characteristic pH (∼4.5-5.0) of lysosomes enables selective probe activation within lysosomes. In this work, a pH-activated K+ nanosensor for lysosomal K+ imaging was designed by capturing Y-typed DNA probe on linker modified gold nanoparticle. The DNA probe could be conveniently prepared by assembling dual fluorophores-labelled G-quadruplex (G4) strand, Sgc8c modified i-motif structure and capturing DNA sequence. The folding capability of G4 in the presence of K+ was inhibited at neutral pH, which prevented fluorescence resonance energy transfer (FRET) between two fluorophores labelled at both ends of the G4. Upon targeted delivery into lysosomes, the conformational change of the i-motif structure was activated by acidic pH, leading to G4 folding and thus K+-dependent FRET signal. Sgc8c modification enhanced target-cell-specific internalization for nanosensor delivery. Both in vitro experiments and in situ lysosomal K+ imaging along with external pharmacological stimuli demonstrated the excellent performance of the proposed K+ nanosensor, which expanded the application of DNA-based probes in subcellular imaging field.
Guangming Li, Ying An, Jiahui Sun et al.· Biosensors & bioelectronics· 0 citations
PURPOSE
This report presents long-term outcomes of third-generation anti-CD30 CAR T-cell therapy in relapsed/refractory (r/r) CD30+ lymphoma patients.
PATIENTS AND METHODS
In this single-arm, multicentre, phase 1/2 trial, patients received lymphodepletion regimen comprising fludarabine and cyclophosphamide, followed by infusion of anti-CD30 CAR-T cells. Primary endpoints included safety and overall response rate (ORR), while secondary endpoints were progression-free survival (PFS) and overall survival (OS).
RESULTS
Forty-four patients were enrolled, including 33 cases of Hodgkin lymphoma. Of 44 patients, 23 achieved complete response (CR) to CAR-T, and 19 achieved PR, resulting in a CR rate of 52.3% and an ORR of 95.5%. The most frequent toxicities were hematologic AEs of grade 3 or higher (68.2% of neutropenia). Cytokine release syndrome occurred in 18 patients (40.9%), with two cases (4.5%) being ≥ grade 3. In the follow-up period, 24 patients underwent auto-HSCT after CAR-T within a median of 3 months. The best ORR was 95.5%, with 27 patients (61.4%) achieving CR. The best CR rate was higher in patients receiving CAR-T followed by auto-HSCT compared to those receiving CAR-T alone (75% vs. 45%). 3-year OS and PFS rates for all patients were 79.0% (95%CI, 66.1%-91.9%) and 74.2% (95%CI, 60.3% -88.1%). Patients receiving consolidated auto-HSCT following CAR-T exhibited significantly longer OS and PFS compared to those treated with CAR-T alone.
CONCLUSION
Third-generation anti-CD30 CAR-T demonstrates high efficacy and a favorable safety profile in r/r CD30+ lymphoma patients. Addition of auto-HSCT following CAR T-cell therapy improves depth of remission and potentially enhances OS and PFS.
Xiangmin Wang, Qing Zhang, Dongmei Yan et al.· Clinical Cancer Research· 0 citations
