Targeting metabolic pathways to counter cancer immunotherapy resistance.

Immunotherapies have revolutionized the treatment of certain cancers, but challenges remain in overcoming immunotherapy resistance. Research shows that metabolic modulation of the tumor microenvironment can enhance antitumor immunity. Here, we discuss recent preclinical and clinical evidence for the efficacy of combining metabolic modifiers with immunotherapies.

Promiscuous CD4 Epitope Clusters Associated With Human Recall Responses Are Candidates for a Novel T-Cell Targeted Multi-Epitope Q Fever Vaccine.

, the causative agent of Q fever, is a Gram-negative intracellular bacterium transmitted via aerosol. Regulatory approval of the Australian whole-cell vaccine Q-VAX® in the US and Europe is hindered by reactogenicity in previously exposed individuals. The aim of this study was to identify and rationally select epitopes for design of a safe, effective, and less reactogenic T-cell targeted human Q fever vaccine.

Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression.

Pancreatic β-cell replacement by islet transplantation for the treatment of type 1 diabetes (T1D) is currently limited by donor tissue scarcity and the requirement for lifelong immunosuppression. The advent of in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells, also referred to as SC-β cells, could eliminate these obstacles. To avoid the need for immunosuppression, alginate-microencapsulation is widely investigated as a safe path to β-cell replacement.

AMD3100 Augments the Efficacy of Mesothelin-Targeted, Immune-Activating VIC-008 in Mesothelioma by Modulating Intratumoral Immunosuppression.

AMD3100 (plerixafor), a CXCR4 antagonist, has been demonstrated to suppress tumor growth and modulate intratumoral T-cell trafficking. However, the effect of AMD3100 on immunomodulation remains elusive. Here, we explored immunomodulation and antitumor efficacy of AMD3100 in combination with a previously developed mesothelin-targeted, immune-activating fusion protein, VIC-008, in two syngeneic, orthotopic models of malignant mesothelioma in immunocompetent mice.

Q-vaxcelerate: A distributed development approach for a new Coxiella burnetii vaccine.

Development of vaccines that are both safe and effective remains a costly and time-consuming challenge. To accelerate the pace of development and improve the efficacy and safety of candidate vaccines for both existing and emerging infectious agents, we have used a distributed development approach. This features the managed integration of individual expert groups having the requisite vaccine platforms, pre-clinical models, assays, skills and knowledge pertinent to a specific pathogen into a single, end-to-end development team capable of producing a new vaccine tailored to that particular agent.

A novel automated screening and interpretation process for cervical cytology using the internet transmission of low-resolution images: a feasibility study.

Background: Transmission over the Internet of low-resolution images acquired by automated screening of cervical cytology specimens has the potential to provide remote interpretation and, hence, centralization of a cytology workforce.

Methods: Liquid-based cervical cytology slides were scanned using the FocalPoint(R) System. Ten black-and-white images that had the greatest probability of containing abnormality were acquired from each of 32 reference slides (16 negative samples, 3 samples of atypical squamous cells of uncertain significance, 5 samples of low-grade squamous intraepithelial lesions [LSIL], 5 samples of high-grade squamous intraepithelial lesions [HSIL], 1 adenocarcinoma in situ sample, and 2 carcinoma samples) and were transmitted as e-mail attachments in JPEG format to remote reading stations.