Stay up to date with news from the Personalised Medicine world!
Welcome to the first Education Newsletter of 2024! We hope your term has been going well so far. This month we take a look at a potential new class of antibiotics, early cancer detection through a blood test, and more! As always, please reach out to us if you have a story you'd like us to include in the next edition.
New in Personalised Med
Optimising drug delivery to tumours using thermosensitive liposomes
Although many small molecules have been developed to target cancer cells, drug delivery to solid tumours remains a challenge due to their highly unstructured vasculature. Drug encapsulation systems and nanoparticles have been developed to combat this, but it has been difficult to develop particles that are both stable in the circulation and also able to penetrate the dense extracellular matrix within the tumour. A recent study suggests that heat-sensitive liposomes in combination with targeted induction of tumour hyperthermia using microwaves could increase drug penetration in solid tumours, targeting drug delivery to only affected areas.
Read more about this here.
New class of antibiotics: tethered macrocyclic peptides
Multi-resistant bacterial strains are becoming increasingly prevalent in the community. Zosurabalpin is a newly identified narrow spectrum antibiotic that has been shown to have activity against CRAB (carbapenem-resistant Acinetobacter baumannii), which can cause serious infections with sepsis and pneumonia that have high mortality. The drug acts by inhibiting an LPS-transporter on the bacterial cell membrane.
Read more about this here.
Blood test for early detection of 18 types of cancer
By comparing plasma samples from healthy individuals and those with early stage cancer, researchers under Novelna, a US-based biotech firm, have identified a set of proteins that could detect cancer early and distinguish between different tissues of origin to identify 18 solid tumour types. The study suggests that the cancer protein is sex-specific, and proposes two sets of protein screens. For individuals with Stage I cancer, the panel could identify 93% of cancers in males and 84% of cancers in females.
Read more about this here.
Deep Dive: Cancer Immunotherapy
Immuno-oncotherapy is an umbrella term used to describe treatments that modulate a patient’s immune system to help fight cancer. Many cancer cells develop mutations that allow them to evade immune destruction by mechanisms including loss of MHC/tumour antigen molecules to prevent recognition by T-cells, expression of immune checkpoint ligands to deactivate T-cells, and secretion of immunosuppressive cytokines. Analysis of the tumour genome allows for personalised immunotherapy treatment plans to be made to target the specific immune evasion strategy found in a patient. Further, immunotherapy can be used to target cells with particular markers for immune destruction, an approach which is now widely used to treat blood cancers.
The idea that host immunity can be boosted to fight cancer has been around for a while - initial studies include the work of William Coley back in 1891, when he found that injecting inoperable tumours with Strep. pyogenes caused them to shrink. The underlying principle here is that introducing the bacteria caused local activation of immune cells, promoting an inflammatory environment within the tumour which increased the probability of killing of cancer cells by the host immune system. A similar concept is used now in neoantigen vaccine therapies, which aim to prime and activate the immune system by introducing immunogenic epitopes of mutant antigens expressed by the cancer cells to the body.
Cancer-immunotherapy can broadly be divided into five main types -
Cellular therapies - this involves infusion of immune cells that are selected for their ability to kill cancer cells, and includes treatments like CAR-T cells and adoptive T cell transfer.
Immune checkpoint inhibitors (ICIs) - these are targeted treatments (typically monoclonal antibodies) that block inhibitory signals from cancer cells at the immunological synapse, resulting in increased killing by immune cells. The most commonly used ICIs are PD-1 and CTLA-4 blockers.
Soluble therapies - these include molecules like Bispecific T-cell Engagers (BITEs) and monoclonal antibodies, which bind to specific surface proteins on cancer cells and mark them for killing by immune cells.
Neoantigen vaccines
Oncolytic viruses - these viruses are engineered to selectively infect cancer cells, causing tumour cell lysis and increasing inflammation in the tumour microenvironment.
The mechanism of action of some of these treatments in the periphery (circulation) and tumour microenvironment (TME), and metabolic barriers to their effective function, are shown in the infographic below.
Source: DePeaux, K., Delgoffe, G.M. Metabolic barriers to cancer immunotherapy. Nat Rev Immunol 21, 785–797 (2021). https://doi.org/10.1038/s41577-021-00541-y
Infographic of the Month
Comparing WGS and NGS for personalised cancer treatment - should NGS remain as standard-of-care?
Source: Akhoundova, D., Rubin, M.A. The grand challenge of moving cancer whole-genome sequencing into the clinic. Nat Med 30, 39–40 (2024). https://doi.org/10.1038/s41591-023-02697-7