Most people who responded to a personalized neoantigen vaccine were alive and still had activated T cells up to six years after surgery.

Post et al. develop a screening method to identify cell-penetrating peptides (CPPs) encoded by human gut microorganisms. They thereby discovered a peptide which preferentially enters cancer cell lines over healthy cell lines.

Abstract. Intracellular delivery of therapeutics remains a major challenge for modern medicine. To enhance intracellular uptake, therapeutics can be delivered with carrier proteins possessing an inherent cell-penetrating activity. There is an increasing need for new cell-penetrating carriers with diverse biophysical properties and mechanisms of action to transport a wide range of therapeutic cargo. As many cell-penetrating proteins and peptides derive from natural proteins, we sought to mine a previously unexplored community, the human gut microbiome, for cell-penetrating sequences. Here, we performed a high-throughput functional metagenomic screen to identify cell-penetrating protein fragments from the human gut microbiome. We identified protein fragments encoded within glycosidase enzymes from members of the Bacteroidetes phylum that mediate internalization into human cell lines when displayed on the surface of nonpathogenic, noninvasive Escherichia coli. We investigate one fragment, dubbed Gh_112, that adheres to human fibronectin, activates multiple endocytic pathways, and specifically promotes uptake of E. coli into multiple cancerous epithelial cell lines rather than healthy epithelial tissue in vitro. Overall, this work demonstrates that the human gut microbiome is a source of cell-penetrating sequences and expands the known repertoire of cell-penetrating carrier systems.

A targeted cancer treatment given via a simple injection under the skin shrank tumours in more than one third of patients with recurrent and/or metastatic head and neck cancer whose disease has stopped responding to standard treatments.

New results from phase Ib/II OrigAMI‑4 clinical trial, by scientists from The Institute of Cancer Research, London, and presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, confirmed tumour shrinkage in 42 per cent of patients treated with the drug amivantamab, alongside encouraging survival outcomes in a group of patients who until now had very limited options. The results, published in the Journal of Clinical Oncology, are based on blinded independent central review (BICR), where outcomes were checked by external experts who did not know which treatment each patient received, helping ensure the results are fair, unbiased, and reliable.

Researchers say the findings provide very strong evidence to support the further development of amivantamab as a potential treatment for head and neck cancer, a disease which affects around 12,800 people in the UK each year and is the sixth most common cancer worldwide.

Oxford University researchers have captured the step-by-step assembly of individual virus-like particles, revealing how simple molecular interactions can reliably build these complex biological structures. The results were published today (September 16) in Nature.

A square peg doesn’t fit a round hole. But what if the peg could change the shape of the hole? A newly developed drug molecule can do something surprisingly similar when binding to its target protein, according to a University at Buffalo-led study published Tuesday (Sept. 15) in Angewandte Chemie International Edition.

The molecule, an inhibitor designed to block activity, initially clashed with a flexible loop in the structure of a protein implicated in cancer and known as p38 delta. This clash would normally hinder binding, but it instead caused the loop to change shape and wrap around the molecule, creating an unusually snug fit.

The molecule represented a 12,000-fold improvement in selectivity for p38 delta and was 110-fold more potent than previously available compounds.