FOLR1 ( Folate receptor alpha )

Importantly, this modular conjugation platform allows for facile replacement of ligands, enabling the rational design of receptor-directed AAV vectors for targeted and cell-specific gene therapy. These findings provide mechanistic insights into capsid-receptor interactions and establish a flexible strategy for precision engineering of AAV-based delivery systems.

Regarding the conjugation type, only trastuzumab deruxtecan, labetuzumab govitecan, sacituzumab govitecan, BYON3521, and SYD1875 used homogeneous conjugation. An interesting observation was that for some ADCs, TAA expression was higher in normal tissue than in the tumor. In summary, our analysis highlights that only a limited number of ADCs incorporate payloads with favorable physicochemical properties and that several ADCs currently under development target TAAs with higher expression in normal tissues than in the corresponding tumors.

Furthermore, we propose an innovative four-part mRNA vaccine approach to balance therapeutic effectiveness with clinical practicalities. Both vaccine formulations showed intense immune stimulation in silico, indicating their potential as promising candidates for immunotherapy against TNBC, which will require further experimental exploration.

Mirvetuximab soravtansine-gynx, an FRα-targeting ADC, has been approved by the FDA and EMA for the treatment of FRα-positive, platinum-resistant ovarian cancer... These findings highlight the critical importance of standardized, validated assays for FRα detection to ensure accurate patient selection for targeted therapies. The study emphasizes the need for further optimization of alternative antibodies before clinical implementation.

Complete resection and advanced stage were suggested as prognostic factors in UCS. FRα and Trop-2 are increasingly recognized as therapeutic targets and their elevated expression levels in the epithelial component of UCS are promising, although not associated with prognosis in this cohort.

These findings highlight the IMS's potential for efficiently discovering high-affinity and high-specificity biomolecular probes. The selected aptamer was successfully applied in a detection assay to quantify FRα, underscoring the system's promise for early ovarian cancer diagnosis.

The temporal effect of 50 μM FBP on DNA breakage and the induction of apoptosis, examined by the TUNEL assay, also supports the hypothesis of FBP-mediated folate deprivation of KB cells. The evidence reported in this study sheds light on the mechanism of FBP cytotoxicity in FR-overexpressing KB cancer cells in culture and suggests possible pathways for the observation of inhibited growth for KB xenograft tumors in vivo.

Functionally, ATG5-knockout CAR-T cells maintained high cytolytic activity when assayed in patient-derived ascites in vitro, and exhibited superior and long-lasting tumor control against ovarian tumors in vivo. Taken together, our results suggest that deletion of ATG5 metabolically primes CAR-T cells for enhanced cytotoxicity in immune-suppressive conditions, thereby improving the therapeutic potential of αFR CAR-T cells for ovarian cancer immunotherapy.

Estimated human dosimetry showed high absorbed dose for tumor and minimal absorbed dose for healthy tissues establishing its safety. In totality, FOLR1-targeted 225 Ac alpha-particle therapy is an efficacious and safe treatment with high feasibility for clinical translation to fight against ovarian cancer.

These findings are hypothesis generating and provide rationale for future clinical trials of ADCs and immune checkpoint inhibitors in VSCC. Results suggest HPV-independent tumors may be immunogenically active.

Our results demonstrate that active targeting of chemotherapy-loaded NPs with a FRα ligand, pemetrexed, enhances tumor targeting and antitumor efficacy in a CRC model.

Crucially, FA-PEG-S-Hu5 completely eliminates hemolytic toxicity. This "folate targeting delivery + TME activation" prodrug strategy is expected to provide a new solution for addressing the off-target toxicities of conventional ICIs.