Selective ablation of dsDNA-specific plasma cells improves lupus nephritis in NZB/W mice.

September 29, 2026| Source: Proceedings of the National Academy of Sciences of the United States of America

Antibodies specific for double-stranded DNA (dsDNA) are thought to play a crucial role in the pathogenesis of lupus nephritis. Plasma cells have emerged as a promising therapeutic target in antibody-mediated diseases. Here, we show that dsDNA oligonucleotides longer than 80 bp and irrespective of their sequence, react with more than 80% of murine and human dsDNA antibodies. With a conjugate of a modified antibody to mouse CD138 and 100 bp dsDNA oligonucleotides, we demonstrate the selective depletion of dsDNA-specific antibody secreting plasma cells in NZB/W mice, a mouse model of lupus nephritis. Two days after injection of the conjugate, up to 80% of the dsDNA-specific plasma cells in spleen, bone marrow, and kidneys of the mice were ablated, presumably by complement or cellular cytotoxicity, targeted to them by their own secreted antibodies. Plasma cells secreting antibodies of different specificities were not affected. Treated mice showed a sustained reduction of dsDNA-specific antibodies in the serum and a significant improvement in proteinuria, i.e., kidney pathology. This demonstration of the therapeutic efficacy of antigen-specific ablation of pathogenic plasma cells offers a unique option for the precise treatment of antibody-mediated diseases.

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Spontaneous gas film expansion at an oil-water interface.

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Health & MedicineNovember 10, 2026

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Health & MedicineNovember 10, 2026

Engineered T cell-agonist chimera for logic-gated STING activation and augmented cancer immunotherapy.

The efficacy of adoptive T cell therapy against solid tumors is markedly hindered by the immunosuppressive microenvironment. Here, we demonstrate that stimulator of interferon genes (STING) activation in tumor-associated macrophages (TAM) enhances the intratumoral infiltration and cytotoxicity of adoptive T cells. We next design a TAM-targeted nanoagonist and engineer a T cell - agonist chimera (SNTC) via covalent surface anchoring, to achieve synchronized biodistribution of STING agonist with a

Health & MedicineNovember 4, 2026

Decoding the regulatory programs governing glioblastoma plasticity.

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Health & MedicineNovember 4, 2026

In vivo CAR-T double knockout screen maps synergistic antitumour gene pairs.

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of haematological malignancies, but its efficacy remains limited by multiple negative regulatory mechanisms intrinsic to T cells 1-4 . Here we perform a high-throughput in vivo CAR-T double-knockout (DKO) CRISPR screen, and identify multiple DKO gene pairs that are both effective and synergistic. The top pair, NR4A1-SOCS3 DKO, has multiple favourable immunological features. Whole-transcriptome profiling and in vivo