Project description:Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette–Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a novel mouse anti-IFN-γ DNA aptamer and observed that intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed novel murine HIC mouse model with little migration into the blood. Our study provides the plausible basis for clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.
Project description:Antibody–drug conjugates (ADCs) are a powerful class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. In this study, we developed novel dual-payload ADC (DualADC) platforms that enable co-delivery of a chemotherapeutic agent for direct tumor cell killing and a toll-like receptor agonist to stimulate antitumor immunity. Using triple-negative breast cancer (TNBC) as a model, we established advanced cysteine/lysine co-conjugation strategies optimized for antibody–drug ratio (ADR) and drug–drug ratio (DDR). These refinements minimized hydrophobicity-induced precipitation, enhanced conjugation efficiency, and improved formulation stability. In vivo evaluations in two xenograft mouse models demonstrated strong antitumor efficacy, highlighting the therapeutic potential of DualADCs as a next-generation approach for synergistic chemo-immunotherapy.