Exosomes are nanoscale vesicles derived from endocytosis, formed by fusion of multivesicular bodies with membranes and secreted into the extracellular matrix or body fluids. Many studies have shown that exosomes can be present in a variety of biological fluids, such as plasma, urine, saliva, amniotic fluid, ascites, and sweat, and most types of cells can secrete exosomes. Exosomes play an important role in many aspects of human development, including immunity, cardiovascular diseases, neurodegenerative diseases, and neoplasia. Urine can be an alternative to blood or tissue samples as a potential source of disease biomarkers because of its simple, noninvasive, sufficient, and stable characteristics. Therefore, urinary exosomes have valuable potential for early screening, monitoring disease progression, prognosis, and treatment. The method for isolating urinary exosomes has been perfected, and exosome proteomics is widely used. Therefore, we review the potential use of urinary exosomes for disease diagnosis and summarize the related literature.

Background: Multiple myeloma (MM) is still an incurable hematological malignancy evolved from asymptomatic monoclonal gammopathy of undetermined significance (MGUS). New evidence suggests that circulating microRNAs (miRNAs) can serve as stable diagnostic biomarkers for MM and MUGS.Methods: Serum miRNAs in MM patients, MUGS patients, and healthy controls (HC) were performed by Agilent Bioanalyzer 2100. MicroRNAs in MM detected as promising biomarkers were validated by using quantitative real‐time PCR (qRT‐PCR). Receiver operator characteristic (ROC) curve and multivariate logistic analysis were used to evaluate the diagnostic value of miRNAs for MM and MUGS.Results: In microarray analysis, the top ten differential expressed miRNAs in MM included miR‐134‐5p, miR‐107, miR‐15a‐5p, miR‐5159‐3p, miR‐1914‐3p, miR‐4723‐3p, miR‐5588‐3p, miR‐6893‐3p, miR‐7106‐3p, and miR‐6722‐5p. Three up‐regulated miRNAs (miR‐134‐5p, miR‐107, and miR‐15a‐5p) were further validated. The elevated expression levels of miR‐134‐5p, miR‐107, and miR‐15a‐5p in qRT‐PCR were increased consistent with microarray analysis. These miRNAs distinguished MM and MUGS from HC significantly. Multivariate logistic analysis showed combination miR‐107, miR‐15a‐5p with Hb, the AUC was 0.954 (95% CI: 0.890‐1.000), sensitivity of 91.3%, and specificity of 93.7% for distinguishing MM from MUGS.Conclusions: These data demonstrate that miR‐134‐5p, miR‐107, and miR‐15a‐5p are potential diagnostic biomarkers in MM and MUGS. Moreover, the combination miR‐107 and miR‐15a‐5p with Hb can distinguish MM from MUGS.

To investigate whether CD155 is an attractive target for T cell-mediated immunotherapy against human bladder cancer, we examined the novel bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) for its ability to redirect activated T cells (ATCs) to target bladder cancer cells was examined. Expression of CD155 was detected by flow cytometry on the surface of bladder cancer cells, including T24 and Pumc-91 cells, and their chemotherapeutic drug-resistant counterparts. ATCs generated from healthy donors were stimulated with anti-CD3 monoclonal antibody, anti-CD28 monoclonal antibody and interleukin-2 (IL-2) for 14 days. The cytotoxic activity of ATCs armed with CD155Bi-Ab against bladder cancer cells was detected by LDH and luciferase quantitative assay. Furthermore, ATCs generated from bladder cancer patients were also armed with CD155Bi-Ab to verity the cell killing by the same methods. In contrast to unarmed ATCs, CD155Bi-armed ATCs against bladder cancer cells were increased cytotoxic activity at effector/target (E/T) ratios of 5:1, 10:1, and 20:1, with more IFN-γ, TNF-α secreting. It is worth noting that in spite of the presence of immunosuppression in bladder cancer patients and the drug resistance in chemotherapeutic drug-resistant cancer cell lines, not only the anti-tumor effect of CD155Bi-armed ATCs generated from bladder cancer patients still showed significantly but only higher level of activation marker CD69 was expressed. Taken together, our results suggest that CD155 is an effective target for the CD155-positive bladder cancer. And CD155Bi-Ab-armed ATCs are promisingly to provide a novel strategy for current CD155-positive bladder cancer therapy.

Objective: B7‐H3 is attractive for cancer immunotherapy with B7‐H3 overexpressed tumors. To explore whether B7‐H3 is an effective target for patients with bladder cancer, anti‐ CD 3× anti‐B7‐H3 bispecific antibodies (B7‐H3Bi‐Ab) was armed with activated T cells ( ATC ) to kill bladder cancer cells. Methods: High expressions of B7‐H3 on human bladder cancer cells were detected, including Pumc‐91 and T24 cells, and their chemotherapeutic drug‐resistant counterparts. ATC generated from healthy donors were stimulated with anti‐ CD 3 monoclonal antibody and interleukin‐2 ( IL ‐2) for 13 days. The ability of ATC armed with B7‐H3Bi‐Ab to kill bladder cancer cells was detected by flow cytometry, LDH , Elisa, and luciferase quantitative assay. Moreover, ATC generated from bladder cancer patients was armed with B7‐H3Bi‐Ab to verity the cell killing by the methods as previously described. Results: Compared with unarmed ATC , a significant increased cytotoxicity of B7‐H3Bi‐Ab‐armed ATC against bladder cancer cells was discovered. The B7‐H3Bi‐Ab‐armed ATC secreted more IFN ‐γ, TNF ‐α, and expressed high levels of activation marker CD 69. Interestingly, despite the presence of immunosuppression in patients and resistance in chemotherapeutic drug‐resistant cancer cell lines, B7‐H3Bi‐Ab‐armed ATC from patients with bladder cancer still showed significant cytotoxic activity against bladder cancer cells and their chemotherapeutic drug‐resistant counterparts. Conclusion: B7‐H3 is an effective target for bladder cancer. B7‐H3Bi‐Ab enhances the ability of ATC to kill bladder cancer cells. B7‐H3Bi‐Ab‐armed ATC is promisingly to provide a novel strategy for current bladder cancer therapy.