Genetic Engineering Publications - GEG Tech top picks

 A phase I clinical trial of an adjuvant personalized mRNA neoantigen vaccine, autogene cevumeran, in patients with pancreatic ductal carcinoma demonstrates that the vaccine can induce T cell activity that may correlate with delayed recurrence of disease.

Cancer vaccines are an active area of research for many laboratories. However, one team of researchers has taken an approach that is distinct from other labs. Instead of using inactivated tumor cells, the researchers are reusing live tumor cells that possess the characteristic of traveling long distances to return to the site of their tumor counterparts. Taking advantage of this unique property, the research team engineered live tumor cells using the CRISPR-Cas9 gene-editing tool and reused them to release tumor cell killing agents. In addition, the modified tumor cells were engineered to express factors that would make them easy for the immune system to spot, tag, and remember, preparing the immune system for a long-term antitumor response. The researchers tested their CRISPR-enhanced, reverse-engineered therapeutic tumor cells (ThTCs) in different strains of mice, including one that carried human-derived bone marrow, liver and thymus cells, mimicking the human immune microenvironment. The researchers also built a two-layer safety switch in the cancer cell that, when activated, eradicates ThTCs if necessary. The promising results are published in Science Translational Medicine. 

A boost for CAR–T cells

Chimeric antigen receptor (CAR)–T cell immunotherapy has been highly successful for treating certain blood cancers. Yet this approach has been a challenge for solid tumors, in part because it is difficult to target functional engineered T cells to the tumor site. Ma et al.designed a vaccine strategy to improve the efficacy of CAR–T cells by restimulating the CAR directly within the native lymph node microenvironment (see the Perspective by Singh and June). Injected “amph-ligand” vaccines promoted synthetic antigen presentation and led to CAR–T cell activation, expansion, and increased tumor killing. The system could potentially be applied to boost any CAR–T cell.

Here, the authors present a dataset containing a genome-wide RNA interference screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine.

Pancreatic cancer is an incurable form of cancer and gene therapies are currently in clinical trials to treat this deadly disease. A comprehensive review of gene and cell biotherapies in development to combat pancreatic cancer is published in the peer-reviewed journal Human Gene Therapy. The article, "Pancreatic Cancer Cell and Gene Biotherapies: Past, Present and Future," by corresponding author Pierre Cordelier of the University of Toulouse, and co-authors describes ongoing gene therapy clinical trials. In addition to gene therapies, the authors discuss vaccines, chimeric antigen receptor (CAR) T-cell therapy, suicide genes and oncolytic viruses.

Treatments based on immunotherapy give hope to many people with cancer that they will finally be cured. However, some treatments can be very expensive, have side effects, or may only work on a small number of people. That's why researchers at the University of Chicago's Pritzer School of Molecular Engineering have developed a new therapeutic vaccine using a patient's own tumor cells that have been modified to secrete vascular endothelial growth factor and then irradiated so that the cells are dead before being reinjected. This vaccine would therefore train the patient's immune system to detect and eradicate cancer because, according to clinical trials, it stops the growth of melanoma tumors in mouse models. In addition, an immunological memory is set up thanks to the vaccine and leads to long-term effects because the vaccine would destroy the appearance of new tumor cells 10 months after the injection. The injection of the vaccine is done like a traditional vaccine. The advantages of this vaccine are that it would be more effective, less expensive and much safer.

n a step forward in the search for an HIV vaccine, Professor Denis Burton and colleagues from the Scripps Institute in La Jolla, California have manufactured an HIV vaccine that, with just one shot, induced six out of 12 monkeys to make antibodies that significantly delayed infection or (in two cases) even prevented it. The findings are published in the 15 January issue of Immunity.

This first-ever demonstration in human beings shows that a prophylactic mRNA-based
candidate vaccine can induce boostable functional antibodies against a viral antigen
when administered with a needle-free device, although not when injected by a needle-syringe.
The vaccine was generally safe with a reasonable tolerability profile.

Researchers have developed an E. coli-based transport capsule designed to help next-generation vaccines do a more efficient and effective job than today's immunizations. The research highlights the capsule's success fighting pneumococcal disease, an infection that can result in pneumonia, sepsis, ear infections and meningitis.