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Purpose: Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for clinical application. Cluster of differentiation 24 (CD24) is over-expressed in several human malignancies, especially in hepatocellular carcinoma (HCC). We aimed to develop a new class of CD24-targeted ADCs for HCC. Methods: DOX was conjugated with G7mAb by a heterobifunctional cross-linker GMBS ( N-[gamma-maleimido butyryloxy] succinimide ester) and further analyzed using HPLC. The targeting specificity and endocytosis of the newly generated ADC, G7mAb-DOX, were characterized using flow cytometry assay, near-infrared fluorescence imaging and laser scanning confocal microscope. The antitumor effects were evaluated in nude mice bearing HCC xenografts. Results: G7mAb-DOX with average two drug molecules per antibody was selectively captured and endocytosed by CD24 (+) tumor cells in vitro. In vivo, the ADC was proved to target tumor tissues, suppress tumor growth and prolong the survival of HCC-bearing nude mice with improved efficacy and less systemic toxicity compared with either G7mAb or DOX single-agent treatment. Conclusion: These studies provide proof of concept for development of DOX-based ADCs which provide a novel approach for HCC-targeted immune therapy in clinical application. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that cancer stem cells (CSCs) are a key occurrence in the process of many human cancers. Lung cancer is the most common aggressive malignancy and cause of cancer death worldwide. The research on lung cancer stem cells has been highlighted for many years. Lung CSCs seem to play a major role in lung cancer metastasis, drug resistance and tumour-self-renewal. MicroRNAs (miRNAs), a class of newly emerging small noncoding RNAs that act as post-transcriptional regulators of gene expression, have been demonstrated to serve as a vital player in fine-tuning a number of biological activities ranging from embryogenesis to programmed cell death as well as tumourigenesis. In recent years, several miRNAs have been highlighted to be specifically expressed in CSCs. The miRNA profile of CSCs is remarkably different from non-stem cancer cells. As such, many miRNAs have been shown to regulate self-renewal and differentiation properties of CSCs. In this review, we present the latest findings on miRNAs that regulate the tumour microenvironment of lung CSCs with the goal to prompt the development of novel therapeutic strategies for patients with lung cancer. [ABSTRACT FROM AUTHOR]

We propose that a C-type lectin receptor, SIGNR-1 (also called Cd209b), helps to condition dendritic cells (DCs) in the gastrointestinal lamina propria (LPDCs) for the induction of oral tolerance in a model of food-induced anaphylaxis. Oral delivery of BSA bearing 51 molecules of mannoside (Man51-BSA) substantially reduced the BSA-induced anaphylactic response. Man51-BSA selectively targeted LPDCs that expressed SIGNR1 and induced the expression of interleukin-10 (IL-10), but not IL-6 or IL-12 p70. We found the same effects in IL-10-GFP knock-in (tiger) mice treated with Man51-BSA. The Man51-BSA-SIGNR1 axis in LPDCs, both in vitro and in vivo, promoted the generation of CD4+ type 1 regulatory T (Tr1)-like cells that expressed IL-10 and interferon-γ (IFN-γ), in a SIGNR-1- and IL-10-dependent manner, but not of CD4+CD25+Foxp3+ regulatory T cells. The Tr1-like cells could transfer tolerance. These results suggest that sugar-modified antigens might be used to induce oral tolerance by targeting SIGNR1 and LPDCs. [ABSTRACT FROM AUTHOR]