Albumin fusion with granulocyte-macrophage colony-stimulating factor acts as an immunotherapy against chronic tuberculosis

A long duration of treatment and emerging drug resistance pose significant challenges for global tuberculosis(TB)eradication efforts.Therefore,there is an urgent need to develop novel strategies to shorten TB treatment regimens and to treat drug-resistant TB.Using an albumin-fusion strategy,we created a novel albumin-fused granulocyte-macrophage colony-stimulating factor(albGM-CSF)molecule that harnesses albumin’s long half-life and targeting abilities to enhance the biostability of GM-CSF and direct it to the lymph nodes,where the effects of GM-CSF can increase dendritic cell populations crucial for eliciting a potent immune response.In this study,we demonstrate that albGM-CSF serves as a novel immunotherapy for chronic Mycobacterium tuberculosis(Mtb)infections by enhancing GM-CSF biostability in serum.Specifically,albumin is very safe,stable,and has a long half-life,thereby enhancing the biostability of GM-CSF.In the lungs and draining lymph nodes,albGM-CSF is able to increase the numbers of dendritic cells,which are crucial for the activation of naive T cells and for eliciting potent immune responses.Subcutaneous administration of albGM-CSF alone reduced the mean lung bacillary burden in mice with chronic tuberculosis infection.While GM-CSF administration was associated with IL-1βrelease from Mtb-infected dendritic cells and macrophages,higher IL-1βlevels were observed in albGM-CSF-treated mice with chronic tuberculosis infection than in mice receiving GM-CSF.Albumin fusion with GM-CSF represents a promising strategy for the control of chronic lung tuberculosis infections and serves as a novel therapeutic vaccination platform for other infectious diseases and malignancies.

Targeted tumor coating with antigenic, CTL-recognizable peptides via Annexin A5 chimeric constructs following chemotherapy redirects adaptive CD8+ T cell immunity for tumor clearance

A common drawback of many cancer immunotherapies,including immune checkpoint blockade,is their reliance on the expression of immunogenic tumor antigens by cancer cells for immune recognition and clearance,which limits their efficacy against cancers with weak antigenicity.1 To overcome this obstacle,we and others have explored strategies to harness the immune responses against nontumor antigens and redirect those immune responses to target tumor cells.2,3,4,5 In particular,we have pioneered a therapeutic strategy fusing tumor-targeting proteins with known antigenic peptide epitopes not naturally expressed by tumor cells,which are flanked by peptide sequences that can be recognized and cleaved by proteases overexpressed in most cancers.2,3 This strategy facilitates the targeted delivery of immunogenic peptides into tumor foci,the release of immunogenic peptides into the tumor microenvironment(TME)via tumor protease cleavage,and subsequent loading of these peptides onto major histocompatibility complex class 1(MHC-I)on the tumor cell surface,allowing the recognition of coated tumor cells by the respective peptide-specific cytotoxic CD8+T lymphocytes(CTLs)for elimination.

Attenuation of liver stiffness in sorafenib-treated patients with advanced hepatocellular carcinoma

Aim: Sorafenib is a multi-tyrosine kinase inhibitor and the standard therapy for advanced hepatocellular carcinoma (HCC). This retrospective study aimed to observe the anti-fibrotic effect of sorafenib in patients with advanced HCC. Methods: Seventeen patients with advanced HCC were recruited. Shear wave velocity (SWV) using acoustic radiation force impulse elastography and non-invasive serum markers for liver fibrosis, such as the aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), the AST to platelet ratio index, the fibrosis-4 index and the Lok index, were recorded at the beginning of sorafenib treatment and 3-6 months after sorafenib treatment in 2014-2015. Results: Nine (52.9%) patients achieved disease control status and 8 had progressive disease after a mean duration of 11.1 months with sorafenib treatment. The mean SWV decreased from 2.37 m/s at the beginning to 1.90 m/s after sorafenib treatment (P < 0.01). This trend was observed in patients with and without liver cirrhosis (from 2.49 to 2.06 m/s, P = 0.06, and from 2.32 to 1.69 m/s, P < 0.05, respectively). Among the non-invasive serum markers, no statistically significant differences were observed except for the AAR in the cirrhotic group. Conclusion: Sorafenib has potential antif-ibrotic effects in patients with advanced HCC.