Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
Synchrotron X-ray Assessment Of Airway Surface Physiology For Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$778,228.00
Summary
We seek a cure or long-lasting therapy for the fatal airway disease in cystic fibrosis. Disease is caused by a shallow and dehydrated airway surface liquid (ASL), allowing bacteria to infect the lung. We can introduce a corrective gene into mouse airways where it can be effective for over 1 yr, but no fast, accurate and non-invasive measurement exists to test if treatments are successful. We will develop methods using synchrotron light to directly measure ASL depth changes in live mouse airways.
Radiostereometric Analysis Of The Effect Of A Large Articulation On Prosthetic Wear And Migration After Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$192,186.00
Summary
At total hip replacement, there has been a recent trend to use prostheses with a larger ball and liner in the socket. This may decrease the risk of post-operative dislocation, but may also increase the amount of wear, leading to bone loss and loosening of prostheses, which may then require replacement. This project will use a special type of x-ray to determine whether wear and movement of these new prostheses is clinically acceptable, so that they can be used with confidence in patients.
The Risks And Benefits Of Contemporary Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$493,530.00
Summary
The number of hip replacements undertaken in Australia is steadily increasing. The most common complications of hip replacements are dislocation and loosening due to bone loss around the implant, requiring complex and expensive revision surgery. This study will investigate the incidence of dislocation and, using a new diagnostic imaging technique, the incidence and amount of bone loss around a relatively new prosthetic material, the outcomes of which are not known despite its increasing use.