THE HIDDEN IMPACT OF INTRAUTERINE GROWTH RESTRICTION IN THE PATHOGENESIS OF METABOLIC SYNDROME: FUNCTIONAL AND STRUCTURAL ALTERATIONS IN RAT VISCERAL ADIPOSE TISSUE.

Background: Individuals born after intrauterine growth restriction (IUGR) have a higher risk of developing metabolic syndrome (MetS) in adulthood. In a rat model, male IUGR offspring exhibit MetS features-including elevated systolic blood pressure, glucose intolerance, non-alcoholic fatty liver disease, and increased visceral adipose tissue (VAT)-by 6 months of age. Female offspring, however, do not.

Validation of the C-X-C chemokine receptor 3 (CXCR3) as a target for PET imaging of T cell activation.

Purpose: CXCR3 is expressed on activated T cells and plays a crucial role in T-cell recruitment to the tumor microenvironment (TME) during cell-based and immune checkpoint inhibitor (ICI) immunotherapy. This study utilized a Cu-labeled NOTA-α-CXCR3 antibody to assess CXCR3 expression in the TME and validate it as a potential T cell activation biomarker in vivo.

Procedures: CXCR3 cells infiltrating MC38 tumors (B57BL/6 mice, untreated and treated with αPD-1/αCTLA-4 ICI) were quantified using fluorescence microscopy and flow cytometry.

Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins.

Cysteine cathepsins are a family of proteases that are relevant therapeutic targets for the treatment of different cancers and other diseases. However, no clinically approved drugs for these proteins exist, as their systemic inhibition can induce deleterious side effects. To address this problem, we developed a modular antibody-based platform for targeted drug delivery by conjugating non-natural peptide inhibitors (NNPIs) to antibodies.

Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release.

Template-directed methods are emerging as some of the most effective means to conjugate payloads at selective sites of monoclonal antibodies (mAbs). We have previously reported a method based on an engineered Fc-III reactive peptide to conjugate a radionuclide chelator to K317 of antibodies with the concomitant release of the Fc-III peptide ligand. Here, our method was redesigned to target two lysines proximal to the Fc-III binding site, K248 and K439.

Influence of corticosteroid treatment on CXCR4 expression in DLBCL.

Background: CXCR4-targeted radioligand therapy (RLT) with [Lu]Lu/[Y]Y-PentixaTher has recently evolved as a promising therapeutic option for patients with advanced hematological cancers. Given their advanced disease stage, most patients scheduled for PentixaTher RLT require concomitant or bridging chemotherapy to prevent intermittent tumor progression. These (mostly combination) therapies may cause significant downregulation of tumoral CXCR4 expression, challenging the applicability of PentixaTher RLT.