CARPETS: A Phase I Open Label Study Of The Safety And Immune Effects Of An Escalating Dose Of Autologous GD2 Chimeric Antigen Receptor-Expressing Peripheral Blood T Cells In Patients With Metastatic BRAF-Mutant And GD2-Positive Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$351,583.00
Summary
Malignant melanoma is increasing in incidence in Australia. Current drugs for advanced melanoma are only sometimes effective. BRAF blocking drugs with promising anti-melanoma activity are being tested in Australia but drug resistance is developing. We will genetically engineer the patient’s own T cells to redirect them against the melanoma. The feasibility, safety, and immune effects of this approach will be tested in patients whose advanced melanoma is no longer responding to BRAF blockers.
Aberrant Transcriptional Signalling In The Progression And Metastasis Of Melanoma.
Funder
National Health and Medical Research Council
Funding Amount
$353,033.00
Summary
There are currently no treatments that have any impact on decreasing mortality from metastatic melanoma. We have found 2 new variants in melanoma that may control the tumour growing and invading around the body. This study will examine the protein containing these changes with the aims of finding how they function differently, to identify their roles in the formation of melanoma, as well as to identify new targets for prevention and treatment of metastatic disease.
Reactivities Of CD8 T Cells To Mutated Neo-antigens In Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
Tumours express mutated proteins (called ‘neo-antigens’) which can be targets of powerful killer T cells which can destroy cancer cells. To understand why these cells fail to cure most cancers we will study neo-antigens identified by modern DNA sequencing methods to identify these neo-antigens & the responses to them. Then it will be possible to design trials in individual patients, e.g. personalised vaccines to ‘force’ the immune system to attack cells bearing these neo-antigens.
Influence Of Skin Cancer On Topical Elongate Microparticle Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$560,589.00
Summary
This project builds on a novel cutaneous delivery method using ‘rod-shaped’ microparticles we developed in the Dermatology Research Centre. Microparticle administration results in multiple punctures of the skin’s tough outer layers, increasing permeability. Furthermore, microparticle administration results in a uniform and continuous drug delivery profile within the treatment area, which is an important attribute for the treatment of skin diseases.
Enhancing Aspects Of Time-to-event Analysis Methodology In Randomised Trials
Funder
National Health and Medical Research Council
Funding Amount
$548,446.00
Summary
Time-to-event analysis is a statistical method for examining the occurrence of disease-related events in individuals followed for varying periods of time. The method is widely used in health research. The technicalities of the methods are subtle and by paying careful attention to these this grant will provide extended methods, new software, and apply methods more effectively to gain new insights to disease progress, and to enhance the efficiency of health research.
Role Of Resident Endothelial Progenitor Cells In Melanoma Vascularisation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$952,328.00
Summary
Melanoma is one of the most frequent cancers in Australia. Its growth depends on the rpoper delivery of nutrients and oxygen through blood vessels. This requires the formation of new blood vessels as the tumour grows. In this project we intend to understand the origin of the blood vessels that form in tumours and identify the stem cells that support them. We will use proof of principle experiments to determine whether removal of these stem cells allows the regression of melanoma tumours.
The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.
Alpha-actinin-4 As An Oncogenic Driver And Therapeutic Target In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$401,786.00
Summary
Despite the recent advances in targeted therapy and immunotherapy, curative treatment of metastatic melanoma remains an unmet health problem. In this project, we will potentially demonstrate that a protein called ACTN4 is abnormally expressed at high levels in melanoma cells and plays an important role for melanoma cell survival and resistance to treatment, and thus identify inhibition of ACTN4, either alone or in combination with other drugs, as a novel approach in the treatment of melanoma.
Genetic Polymorphisms Associated With Clinical And Dermoscopic Naevus Signature Patterns
Funder
National Health and Medical Research Council
Funding Amount
$842,841.00
Summary
Melanoma is a form of skin cancer that arises from the cells that produce pigment and is a major public health issue in Australia. We will examine the relationship between the form, structure and colour of existing types of moles and their subsequent risk of developing into melanoma. This study will combine dermoscopy, a non-invasive examination technique, with DNA tests of the genes that determine number of naevi, skin, hair and eye colour, aiding in the early prediction and diagnosis of skin c ....Melanoma is a form of skin cancer that arises from the cells that produce pigment and is a major public health issue in Australia. We will examine the relationship between the form, structure and colour of existing types of moles and their subsequent risk of developing into melanoma. This study will combine dermoscopy, a non-invasive examination technique, with DNA tests of the genes that determine number of naevi, skin, hair and eye colour, aiding in the early prediction and diagnosis of skin cancer.Read moreRead less
Significance Of Soluble PD-L1 In Melanoma Patients
Funder
National Health and Medical Research Council
Funding Amount
$561,236.00
Summary
A class of new immunotherapy drugs called “antibodies of immune checkpoints” can lead to long-lasting melanoma regression, but they are only beneficial to a subset of patients. This project will potentially identify the increased expression of a protein called PD-L1 in the blood as a biomarker predictive of responses of melanoma patients to these new drugs. The results will be instructive for selection of patients for the treatment.