CD44v3 And V6 As Targets For Anti-metastasis Therapy
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Cancer metastasis remains the principal cause of treatment failure in malignant disease. Current therapies for metastases are generally non-specific, and can cause considerable systemic toxicity. The ideal target for metastasis therapy would be expressed by a broad range of tumours, but be restricted in expression in normal tissues. CD44 is a family of widely expressed cell-surface adhesion molecules and its members are implicated in a variety of physiological and pathological processes, includi ....Cancer metastasis remains the principal cause of treatment failure in malignant disease. Current therapies for metastases are generally non-specific, and can cause considerable systemic toxicity. The ideal target for metastasis therapy would be expressed by a broad range of tumours, but be restricted in expression in normal tissues. CD44 is a family of widely expressed cell-surface adhesion molecules and its members are implicated in a variety of physiological and pathological processes, including tumour progression and metastasis. CD44 has considerable molecular diversity and its broad range of known biological activities suggests that multiple domains in the molecule may confer different biological functions. The core CD44 molecule, termed CD44s, is the most commonly expressed CD44 molecule. CD44 variants (termed CD44v) are much more restricted in their expression in normal tissues, and hence may make specific targets for anti-metastasis therapy. We have shown that CD44 variants are expressed by colorectal tumours from the earliest stages of tumour development, and that theses variants are found to be expressed by colorectal hepatic metastases. We targeted two key domains in the variants and found that by inhibiting expression in these domains we showed complete abrogation of metastasis, and of primary tumour growth in mice. Hence these domains in the CD44 molecule are directly involved in cancer spread. We propose to develop a number of specific methods of targeting CD44 in order to prevent the spread of cancer. We have and will develop additional agents directed to these key domains in CD44. Targeting these domains has great potential as metastasis therapy.Read moreRead less
A New Scrambled Antigen Vaccine (SAVINE) Approach: Proof-of-concept In Non-human Primates For HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$120,700.00
Summary
The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of H ....The specific aim of this proposal is to demonstrate, in non-human primates, proof–of-concept of a patented new platform vaccine technology (scrambled antigen vaccine or SAVINE) designed to encode all the protein sequences of an infectious agent, in this case HIV-1. These are arranged as equal-sized, overlapping fragments such that all potential T cell epitopes that are needed to induce broad T-cell-mediated immunity are maintained. The synthetically designed vaccine uses consensus sequences of HIV-1 to provide universal coverage of the major HIV-1 strains for a global population. The synthetic systematically designed HIV-1 vaccine will be delivered using our newly developed prime-boost immunisation regime that induces particularly high levels of cell-mediated immunity.Read moreRead less
Hypoallergenic Proteins As Novel Immunotherapeutic Candidates For Food Allergy
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
The rate of food allergy has tripled over the past decade and is a leading cause of food related anaphylaxis in Australia. Allergen immunotherapy can help patients develop tolerance to the allergenic food. This research will investigate the potential of hypoallergenic derivatives of two major food allergens as novel desensitisation therapeutics, addressing an issue of significant importance to human health, paving the way for research on advanced therapeutics for paediatric food allergy.
Characterisation Of A Novel Direct Electrochemical Chip As A Biosensor And Tool For Studying Redox-sensitive Proteins
Funder
National Health and Medical Research Council
Funding Amount
$144,500.00
Summary
Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advanc ....Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advance in biosensing capabilities using a recombinant protein (thioredoxin) and demonstrated the improvement that is possible by (i) immobilising the protein in a highly oriented way and (ii) using a sensitive electrical signal to monitor the response. Here we will undertake more comprehensive testing by extending the number of proteins to include the 4 major classes of redox-sensitive biomolecules (proteins) in the body. This will enable us to establish the broad application of our methods and substantially improve our ability to commercialize our discoveries.Read moreRead less