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MT23 Education Newsletter

Stay up to date with news from the Personalised Medicine world!

This is a monthly newsletter where we bring you highlights of recent news from the Personalised Medicine space and a short deep dive into a sub-area of the field.

Please feel free to contact us if you have a story you'd like included in the next edition!


New in Personalised Med

Modified CRISPR-Cas9 protocol reduces chromosome loss, improving outcomes in CAR-T cell trial

The use of CRISPR-Cas9 to genetically engineer T cells for cancer immunotherapy by inserting a transgene for Chimeric Antigen Receptor (CAR) expression is an active area of research. CRISPR technology allows for gene editing with high accuracy; however, potential off-target interactions remain a concern, and chromosome loss with the potential for genotoxicity has been reported in pre-clinical CAR-T cell trials. A research team led by the Doudna lab has recently found that the probability of chromosome loss occurring after CRISPR-Cas9 editing can be significantly reduced (from 55% to less than 1%) by swapping two of the steps in the protocol.

Read more about this here

Machine-learning model expedites CNS tumour classification, assisting in quick decision making during surgery

Surgical resection is the primary treatment available for CNS tumours, but also poses major risk of neurological damage to the patient. The tumour type, including which part of the brain the tumour is derived from and what specific genetic mutations are present, is an important factor when calculating the optimal extent of resection. A neural network model has been developed to predict CNS tumour type on the basis of the methylation profile of a small brain tumour sample, allowing for tumours to be classified intraoperatively (<90 mins). This could reduce the need for additional surgeries and prevent neurological co-morbidities in patients.

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Personalised cancer vaccine passes Phase II clinical trial

Personalised cancer vaccines are a type of therapeutic vaccine devised from the neoantigens found in an individual patient’s tumour. The underlying principle is that vaccination with the neoantigen will prime the patient’s immune system, making it more effective at killing tumour cells. A Phase II clinical trial by Moderna for their personalised melanoma vaccine vaccine mRNA-4157 has shown positive results published earlier this year, with the Phase III trial soon to be underway. While this is still preliminary data, clearing the first clinical hurdle is promising and leaves the community optimistic about the future of personalised vaccines and immunotherapy.

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3D printing method shows potential to repair brain injury in murine model

An Oxford-based research group have been able to grow a two-layered brain tissue sample by 3D printing human neural stem cells. The sample mimicked the complex cytoarchitecture of cerebral cortical columns, and remained structurally intact when integrated with an ex vivo lesioned mouse brain slice. This is an exciting step towards the creation of personalised implants for repair of brain trauma.

Read more about this here


Deep Dive: Microbiome in Diagnostics

The gut microbiome refers to the microorganisms, including bacteria, archaea, fungi, and viruses that live in your digestive tract. These microbes can be both helpful and potentially harmful. Most of them tend to be symbiotic, but a small proportion of them are pathogenic. However, in a healthy body these can coexist without problems.

Microbiome-based diagnostics is the name given to the tools that allow detection of human disease using microbial signature. This is different to classic microbiological tests for infectious diseases because what these tests typically aim to confirm is the presence of a target microorganism. What microbiome-based diagnostics does is identify a microbial signature – the presence, absence, or abundance of certain microbes and/or microbial activities) of different types (e.g. DNA, RNA, proteins or other metabolites), alone or in combination with other biomarkers (e.g. human genetics or metabolites), to detect disease and/or make prognoses. They are the result of the qualitative and quantitative integration of trans-kingdom, multi-omics biomarkers.

A key next step in using the microbiome to diagnose disease is to establish microbiome-encoded disease phenotypes. When we use genetics to diagnose things and make predictions, we benefit from the fact that your genes are relatively stable, particularly compared to microbial genomes. Polymorphisms can be traced and associated using genome-wide association studies (GWAS) for complex diseases and other data to classify phenotypes. Although multiple studies have shown an association between microbiome signatures and diseases, there are certain difficulties in proving causation as opposed to just correlation. To make a true link between microbiome and disease is complex and requires a wide range of statistical testing and sampling. Another issue is that observation of taxonomic association with certain disease states does not always agree between studies. This is potentially because there is a large degree of heterogeneity from both host and environmental factors that contribute to the establishment and maintenance of the microbiome over the course of a patient’s life. However, despite these challenges, microbiome-wide association studies (MWAS) and other approaches are revealing microbiome contributions to human health and disease. Many diseases are impacted by the microbiomes capacity to modulate the immune system, specifically in its ability to influence levels of inflammation in the gut.

One particular study looks at the role of the microbiome in cancer development, and how this information can be used in treatment. The microbiota of each human body organ is unique, and its effects on inflammation and cancer are also distinct in each organ. By understanding the changes in microbiome, and the frequency of various microbial population in different positions in organs we can gather information potentially related to the development of diseases such as cancer. These differences may be responsible for the occurrence of cancer in a particular organ, for example, the susceptibility to colorectal cancer has been linked to the presence of higher microbial density, compared to the small intestine. The microbiome is responsible for various clinical outcomes, and the drug response of individuals can be due to these differences; not all patients show the same response to anticancer therapies. Therefore, given the consideration of each person’s genetic information, and the improvement of drug responses, the personalised therapeutics can play a prominent role in the health care program, especially in relation to cancer.

The ever-increasing understanding of how the microbiome affects health and disease clearly suggests that human microbiome data should be included in precision medicine approaches. The implementation of next-generation sequencing strategies as a means to profile the entire microbial composition at a given body site has accelerated the study of the networks of microbes, the genomic content of which outnumbers the host-encoded functions in a given individual by at least an order of magnitude. Overall, the microbiome could have an important role in personalised medicine. The presence of specific strains may have the ability to modulate cancer progression and therapeutics, which increases the likelihood that precision medicine will successfully treat a disease.


Infographic of the Month

Last week, the FDA evaluated exa-cel, a CRISPR-Cas9 based therapy for Sickle Cell Anaemia. Sickle cell disease is a haemoglobin disorder. The infographic above shows how this treatment, which could become the first FDA approved gene editing therapy for the disease, works.

Source: Bourzac, K. Gene therapy: Erasing sickle-cell disease. Nature 549, S28– S30 (2017).

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