Journal: Journal of Nanobiotechnology

Article Title: Engineering BiTE-inspired IPSC-exosomes to potentiate CAR-T cell therapy against lung cancer

doi: 10.1186/s12951-026-04242-3

Figure Lengend Snippet: BIEXO@IPA platform for enhanced CAR-T therapy in lung cancer. In this study, iPSCs were lentivirally transduced with anti-PD-1/MSLN scFv to generate iPSC lines expressing the engineered construct (BiPSC). BIEXOs were isolated and concentrated from BiPSC culture supernatant via ultracentrifugation, then loaded with IPA through electroporation to form BIEXO@IPA. This platform was nebulized into orthotopic lung cancer mouse models for targeted delivery. In the lung TME, BIEXO@IPA bridges endogenous PD-1 + CD8 + T/CAR-T cells to MSLN-expressing tumor cells while blocking PD-1/PD-L1 signaling and exerting antitumor effects via : (1) BIEXO reverses tumor cell malignancy; (2) IPA delivery enhances Tpex and effector T cells (Teff); (3) activated Teff-mediated cytotoxicity

Article Snippet: Recombinant human PD-1 protein (5 μg/mL, R&D Systems, 1086-PD) was used for capture.

Techniques: Transduction, Expressing, Construct, Isolation, Electroporation, Blocking Assay

Journal: Journal of Nanobiotechnology

Article Title: Engineering BiTE-inspired IPSC-exosomes to potentiate CAR-T cell therapy against lung cancer

doi: 10.1186/s12951-026-04242-3

Figure Lengend Snippet: Functional characterization and T-cell bridging activity. ( a , b ) Binding affinity analysis of engineered exosomes (MIEXO, PIEXO, BIEXO) to MSLN (a) and PD-1 ( b ) via indirect ELISA. Exosomes were added to PD-1 or MSLN-coated plates and detected via an HRP-conjugated anti-His-tag antibody. ( c , d ) Flow cytometric analysis of engineered exosomes (100 µg/mL) binding to PD-1 + T cells ( c ) and LLC-MSLN cells ( d ), with His-tag mean fluorescence intensity (MFI) quantification (right panel). ( e , f ) Confocal microscopy analysis of BIEXO targeting to PD-1 + T cells ( e ) and LLC-MSLN cells ( f ). ( g ) Representative confocal microscopy images and corresponding quantification showing BIEXO-mediated bridging between PD-1 + T cells and LLC-MSLN cells. ( h ) FRET analysis of dose-dependent bridging efficiency. ( i , j ) Prevention of PD-L1-induced T-cell exhaustion measured by LDH release ( n = 3). ( k , l ) Experimental design (k) for ex vivo culture of CD8 + T cells isolated from mouse spleen, and flow cytometric analysis of TCF-1 + Tpex cell expansion in PD-1 + CD8 + T cells following pre-treatment with the AhR antagonist CH-223,191 and BIEXO@IPA stimulation ( l ). ( m ) In vitro growth inhibition of LLC-MSLN cells following treatment. ( n ) Enhanced cytotoxicity of TILs isolated from LLC-MSLN tumor-bearing mice against LLC-MSLN cells following BIEXO@IPA treatment. Data are presented as mean ± SD. Statistical significance was determined using one-way ANOVA followed by Tukey’s multiple comparisons test (c, d, j, m, n). * p < 0.05 , ** p < 0.01 , *** p < 0.001 , **** p < 0.0001

Article Snippet: Recombinant human PD-1 protein (5 μg/mL, R&D Systems, 1086-PD) was used for capture.

Techniques: Functional Assay, Activity Assay, Binding Assay, Indirect ELISA, Fluorescence, Confocal Microscopy, Ex Vivo, Isolation, In Vitro, Inhibition