Avid Bioservices Inc (CDMO)

[biopharm]

Flipped PS and the cargo boards exosomes...and I'll have to say I arrived at ISEV in a prior post but did not come across Dr. Aled Clayton's name.... so from two starting points, this one I was basically starting from Cardiff, due to the passing of Chris MgGuigan .... and simply amazed at the intersection of flipped PS/Exosomes and now Cardiff sits square in the middle of the very first group investigating exosomes and Founding Member of the International Society for Extracellular vesicles (ISEV).

What I do not now just yet was if Chris McGuigen was working with Aled Clayton...... not that it means anything just yet or not but just tossing some puzzle pieces out there and some interesting info regarding exosomes further below, especially => Importantly, however, we may utilise this natural cargo-delivery mechanism to our advantage by loading exosomes with therapeutic molecules. and with the most recent patent between UT System <> Peregrine, I will continue to be completely shocked by those that refuse to believe that there is a good chance that PS Targeting/Peregrine Pharmaceuticals will become a blockbuster due to PS Targeting therapeutic molecules.

Dr. Aled Clayton:

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I established the first group investigating the roles of extracellular vesicles (exosomes) in cancer in the UK.The group has published well over 30 papers in relation to vesicles, and their roles in subverting immune responses, in controlling the cancer microenvironment and as potential disease biomarkers.

I am interested in understanding the mechanisms by which vesicle biogenesis and secretion is controlled, and the impact such vesicles have on the development and progression of cancer; particularly focussing on prostate cancer. Developing tools and assays to quantify nano-vesicles in biological fluid specismens is also an important aspect of the group's activities.

The laboratories are based at the Velindre Cancer Centre, the principal cancer treatment hospital in Wales, and are equipped with specialist instrumentation geared towards the study of exosome-vesicles.

Although my main focus is in cancer biology, I collaborate broadly with researchers in Cardiff and other Universities, on aspects including cardiovascular disease, neurodegenerative diseases and other conditions that impact our society in significant ways.
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Founding Member of the International Society for Extracellular vesicles (ISEV)
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http://www.cardiff.ac.uk/people/view/122903-clayton-aled

http://isev.org/

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Characterising exosome uptake for elucidating their role in cancer progression and as potential drug delivery vectors

Student: Alex Cocks

Supervisor: Dr Aled Clayton Co-Supervisors: Professor Arwyn T Jones and Dr Pete Watson, Institute of Cancer & Genetics, Cardiff University Start Date: Oct 2015

Cancer cells produce and release tiny bubbles of fat called exosomes. These accumulate in fluid around the cells and act in several ways to promote disease: they inhibit the immune system, encourage blood vessel formation (supporting cancer growth), and also activate surrounding cells (called stroma) making the cancer more aggressive. These fat bubbles are analogous to miniature biological parcels, packed with important cargomolecules that are taken inside neighbouring cells to control their behaviour. This cellular uptake is thought to be critical in how exosomes work, however the mechanism of exosome uptake, and where in the cell the cargo is delivered to is not well understood. Importantly, however, we may utilise this natural cargo-delivery mechanism to our advantage by loading exosomes with therapeutic molecules. This would be an exciting new way of delivering active drugs through cell membranes to the insides of target cells to elicit a therapeutic response. Fundamental to identifying their role in cancer and also drug delivery is an understanding of their interaction with cells and their fate inside cells. The study will investigate the details of exosome uptake by cells, and utilise this as a means of delivering therapeutics to cancer cells. It will bring together established expertise in exosome-biology (AC), drug delivery (ATJ) and state of the art microscopy (PW). Together, this expertise will address some very poorly understood questions in the field of cancer exosomes, providing fundamental new insights about how cancers grow and spread and how they could be manipulated to deliver drugs.

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Development of novel Antibody Drug Conjugates for oncology applications

Student: David Howard

Supervisor: Professor Steve Conlan Co-Supervisors: Professor Christopher McGuigan, Dr Deyarina Gonzalez and Dr Lewis Francis Institute of Life Science, Swansea University Start Date: Oct 2015

Despite recent breakthroughs in oncology, many cancers are still incurable and cancer remains the leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Most anticancer drugs, including nucleoside analogues, currently in use are dosed at suboptimal concentrations, are highly toxic and nonspecific attacking both cancer and normal cells. In addition, nucleoside analogues require nucleoside transporters to enter the cells and exert their toxic action. Deficit of nucleoside transporters expression by cancer cells contributes to cancer resistance to nucleoside treatment. Novel nucleoside analogues named ProTides with a high cytotoxic activity can enter the cells freely without the aid of transporters. However, a need remains for the delivery of these drugs directly into the cancer cells without targeting healthy cells. Antibody Drug Conjugates (ADC) are novel drugs that can kill cancer cells while sparing normal cells. ADC molecules consist of an antibody and a drug married together through a linker. Chemical bonding of the drug to the antibody inactivates the drug so that it is not toxic while in circulation. The antibody then delivers the drug to the antigen-expressing cancer cell, where internalization of the ADC occurs, releasing the drug in its active form to kill the targeted cancer cells. This project will profit from the specifity of the antibody part of the ADC and the cytotoxic activity of nucleoside analogues and ProTide derivatives to create novel ADC molecules for oncology applications. The anti-tumour activity of these newly synthesised ADC drugs will be also characterised in cancer cell lines.

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http://www.tenovuscancercare.org.uk/research/laboratory-research/current-phd-student-projects/