Dengue virus (DENV) envelope protein domain III (EDIII) is a premier target for vaccine design because EDIII-specific antibodies can potently neutralize DENV with a low propensity for inducing antibody-dependent enhancement (ADE). We previously identified a cross-reactive antibody, R3N_2D3, which targets the EDIII AG-strand epitope and neutralizes all four DENV serotypes with low ADE, a desirable combination of activities among anti-DENV antibodies. In this study, we expanded this AG-strand-targeting antibody panel by identifying four additional anti-EDIII antibodies from our dengue-immune single-chain variable fragment (scFv)-phage libraries. Despite variations in their binding footprints, these new antibodies converged on key residues within the AG-strand epitope. When expressed as full IgG1, these candidates showed potent cross-neutralization with subnanomolar focus reduction neutralization titers (FRNT50 values) and consistently low ADE compared to the prototypical fusion-loop antibody 4G2 when tested in an in vitro U937 monocytic cell model. Collectively, these findings demonstrate that the AG-strand epitope can elicit broadly protective antibodies with reduced ADE risk, highlighting its potential as a strategic epitope for pan-DENV vaccine development.
Napon Nilchan, Anunyaporn Phungsom, Mongkhonphan Tantiwatcharakunthon et al.· ACS Omega· 0 citations
Colorectal cancer treatment remains limited by poor tumor selectivity, systemic toxicity, and insufficient delivery of combination therapies to three-dimensional tumor-like structures. This study investigates the development and application of anti-carcinoembryonic antigen (anti-CEA) conjugated polymeric nanoparticles co-loaded with sunitinib (SUN) and resveratrol (RSV) for the treatment of colorectal cancer. The nanoparticles, formulated using poly(lactic-co-glycolic acid) (PLGA), exhibited favorable physicochemical properties, including a particle size of 207.6 ± 19.0 nm and a negative surface charge of -24.8 ± 0.7 mV. The nanoparticles exhibited controlled and sustained drug release, enabling the prolonged therapeutic efficacy of SUN and RSV. Functionalization with anti-CEA antibodies enabled selective targeting of colorectal cancer cells, as demonstrated by enhanced internalization in HCT-116 cells with high CEA expression. Consistent with this targeting effect, the anti-CEA-conjugated nanoparticles achieved a 29% relative reduction in cell viability against HCT-116 cells compared to non-targeted counterparts in two-dimensional cultures. Furthermore, the SUN and RSV combination exhibited potent synergistic effects across three-dimensional spheroid models. The anti-CEA functionalized system proved more effective, reducing spheroid volume and cell viability by 10% and 14%, respectively, compared to the non-targeted nanoparticles. These findings highlight the potential of CEA-targeted polymeric nanoparticles for co-delivery of synergistic anticancer agents, offering a promising strategy for colorectal cancer therapy.
Punnida Nonsuwan, Kanyanut Insawang, Nattarika Niwetbowornchai et al.· International Journal of Bio...· 0 citations
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