Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery

Background Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m). Results Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n. Conclusion DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy. Graphical Abstract

Antibodies targeting surface membrane antigens in patients with chronic graft-versus-host disease

Key Points Patients with cGVHD develop antibodies targeting cell membrane antigens. Targeted antigens are broadly expressed in acute myeloblastic leukemia cells and in tissues affected by cGVHD.

Naturally produced opsonizing antibodies restrict the survival of Mycobacterium tuberculosis in human macrophages by augmenting phagosome maturation

This study investigated the hypothesis that serum antibodies against Mycobacterium tuberculosis present in naturally infected healthy subjects of a tuberculosis (TB) endemic area could create and/or sustain the latent form of infection. All five apparently healthy Indian donors showed high titres of serum antibodies against M. tuberculosis cell membrane antigens, including lipoarabinomannan and alpha crystallin. Uptake and killing of bacilli by the donor macrophages was significantly enhanced following their opsonization with antibody-rich, heat-inactivated autologous sera. However, the capability to opsonize was apparent for antibodies against some and not other antigens. High-content cell imaging of infected macrophages revealed significantly enhanced colocalization of the phagosome maturation marker LAMP-1, though not of calmodulin, with antibody-opsonized compared with unopsonized M. tuberculosis . Key enablers of macrophage microbicidal action—proinflammatory cytokines (IFN- γ and IL-6), phagosome acidification, inducible NO synthase and nitric oxide—were also significantly enhanced following antibody opsonization. Interestingly, heat-killed M. tuberculosis also elevated these mediators to the levels comparable to, if not higher than, opsonized M. tuberculosis . Results of the study support the emerging view that an efficacious vaccine against TB should, apart from targeting cell-mediated immunity, also generate ‘protective’ antibodies.

Expression of Cell Membrane Antigens in Cells Excreted in the Urinary Sediment Predicts Progression of Renal Disease in Patients with Focal Segmental Glomerulosclerosis

Background/Aims: A link between the number of podocytes excreted in the urine and activity of glomerular disease has been established. The aim of this study was to investigate possible correlations between urinary cells' phenotype and the progression of focal segmental glomerulosclerosis (FSGS). Methods: Forty patients with newly diagnosed FSGS were included. Cells were isolated from urine by adherence to collagen-coated cover slips and assessed for the expression of podocalyxin (PDX), CD68 and Ki67 antigens by indirect immunofluorescence. In addition, double-staining procedures were performed in combinations of the above antigens plus cytokeratin, WT1 and CD-105. Twenty-two patients in whom urinary protein to creatinine ratio exceeded 2.0 at diagnosis were followed for 36 months, with assessments of renal function and proteinuria every 3 months. During observation, patients were subjected to standard therapy. Results: Significantly higher numbers of Ki67 positive cells at the onset of the study were observed in patients who have doubled serum creatinine (SCr) in follow-up, than in those who have not (p = 0.0149). By logistic regression analysis, both CD68 and Ki67, but not anti-PDX positive cell numbers at diagnosis were found to be predictors of doubling SCr concentration in 36 months' follow-up. Results of double staining indicate that PDX positive cells could be identified as podocytes or their precursors and parietal epithelial cells. Conclusion: Urinary sediment PDX positive cell numbers do not predict the progression of FSGS, whereas CD68 and Ki67 phenotype of urinary podocytic lineage clearly has a prognostic significance in 36 months' observation of primary FSGS.

Antineuronal autoantibodies in neurological disorders

Autoantibodies (abs) related to neurological disease are currently classified into two large groups depending on the site of the respective target antigen: Group I encompasses abs that recognise intracellular antigens (Hu, Yo, Ri, CV2/CRMP5, amphiphysin, Ma2, SOX, ZIC, GAD, adenylate kinase 5, homer 3), whereas group II abs are targeted against neuronal cell membrane antigens (VGKC, AMPA-R, GABAB-R, NMDA-R, Glycine-R, VGCC, metabotropic GluR1). Both abs groups can be further subdivided according to their diagnostic impact for paraneoplastic or non-paraneoplastic neurological disease. The review gives an overview of the common characteristics of each group and provides more detailed information on single abs and the associated clinical syndromes.