Recent medical research from the Malaghan Institute

Regan Fu

Dr Regan Fu recently completed his doctoral thesis on cancer immunotherapies through hypoxia-activated drugs. Photo: Malaghan Institute.

The Malaghan Institute of Medical Research is not only spear-heading the Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo, New Zealand’s COVID-19 vaccine programme, but their researchers have also recently published a slew of research results across a broad spectrum of programmes.

In allergy research, new findings about how the immune system responds to threats moves us closer to more targeted treatments for allergies and autoimmune disorders and more effective vaccines; also in allergy and autoimmune research another group has been investigating the therapeutic potential of human hookworms – which subdue the immune system (inflammatory and autoimmune diseases are characterised by an overactive immune system); new PhD research into cancer drugs could provide the means to deliver higher doses of anti-cancer drugs in oxygen-poor environments; and in immunology research a team have uncovered a novel way Mānuka honey helps stimulate the immune system to fight bacteria.

Immune system discovery could lead to better treatments and vaccines

New findings about how the immune system responds to threats is taking us one step closer to more targeted treatments for allergies and autoimmune disorders and more effective vaccines.

The research, funded by the Health Research Council of New Zealand and recently published in Nature Communications, reveals that the same subset of immune cells – dendritic cells found on the skin – can start different types of immune responses depending on the conditions they are exposed to. It was previously thought that different populations of dendritic cells were responsible for initiating different immune responses in the body.

“We wanted to better understand how different types of immune response start,” says the Malaghan Institute’s Professor Franca Ronchese.

“Parasites, allergens, other pathogens – they all elicit a distinct response. We know roughly what kinds of immune cells are involved in the response, but how they get going, how they arrange themselves, and how they respond to different stimuli is worth investigating given the implications for vaccine design and for redirecting immune responses when they go rogue or overreact.”

Prof Ronchese says the new knowledge could ultimately enable gentler, more targeted therapies for diseases caused by an over-reaction of the immune system.

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Cancer immunotherapies through hypoxia-activated drugs

A recurring issue with many cancer immunotherapies is the difficulty of delivering the cancer-killing drug to the heart of a tumour. The internal environment of a tumour can be very different from the rest of the body, which helps the tumour resist treatment. Many tumours are ‘hypoxic,’ or oxygen-poor, making it hard for immune cells and cancer drugs to infiltrate a tumour, and on occasion even suppressing the immune response to the cancer entirely.

Dr Regan Fu, who recently completed his doctoral thesis with Professor Ian Hermans, is assessing immunotherapies in combination with the hypoxia-activated drug tarloxotinib. Through adding a hypoxic trigger that activates in the oxygen-poor intratumoral environments, higher doses of anti-cancer drugs can be delivered.

Hypoxia-activated drugs are also much more tumour-specific, resulting in less damage to healthy tissues surrounding the tumour. Future work is planned to better understand how tarloxotinib interacts with the immune system, with the aim of moving towards clinical trials.

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Hookworm therapy study expands to treat allergic inflammatory diseases

Clinical research into the therapeutic potential of human hookworms is shifting up a gear. The programme, which will run a number of clinical trials in patients with allergic and inflammatory disease over the next few years, comes off the back of the Institute’s initial and ongoing study investigating how human hookworms alter their host’s health and immune system profile.

“Hookworms have evolved over millions of years to manipulate their host’s immune system in order to survive, dampening down the human immune system to evade detection and expulsion,” says Professor Graham Le Gros, Director of the Malaghan Institute. “And most importantly they seem able to do this without negatively affecting the human host when administered at the right dose.”

“This offers huge therapeutic potential. Inflammatory and autoimmune diseases are characterised by an overactive immune system, so subduing this kind of response is an obvious line of treatment.”

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MAIT cells and mānuka honey – scientists uncover novel antibacterial mechanism

The Malaghan Institute, in collaboration with the Ferrier Research Institute, have uncovered a novel way mānuka honey helps stimulate the immune system to fight bacteria. The team have recently published their findings in the Royal Society of Chemistry’s Food & Function journal, identifying that one of the main bioactive components in mānuka honey could help activate specific bacteria-fighting immune cells. The research is partly funded by the High-Value Nutrition Ko Ngā Kai Whai Painga National Science Challenge.

Honey is a complex natural product known to have strong antibacterial properties. Unlike regular honey which contains trace amounts of hydrogen peroxide as its main antibacterial component, Mānuka honey contains the molecule methylglyoxal (MGO). The amount of MGO in Mānuka honey gives Mānuka products its MGO rating.

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Date posted: 24 November 2020

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