Human Dendritic Cell Subsets And Their Application For Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
Immunotherapy is a promising non-toxic strategy for the treatment of many cancers, viruses and other diseases. It works by teaching the patient's own immune system to recognize and destroy the cancer. Specialized blood cells called dendritic cells are essential to this process but they are poorly understood in humans. I aim to investigate the function these cells and use this information to develop new treatments for cancer and viruses.
Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models ....Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models. We now propose to refine this technique in animals in preparation for human clinical trials.Read moreRead less
My research is aiming to study how the immune system controls viral infections in transplant patients and use this information to bolster their immunity in a test tube, providing protection against a virus the patient is unable to fight after their transplant. We are also trying to develop new strategies to use patient's own blood cells which will be grown in the laboratory and returned to the patient, resulting in a full recovery.
TARGETING THE HUMAN CROSS-PRIMING DENDRITIC CELLS FOR IMMUNOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Specialized white blood cells called dendritic cells (DCs) are essential to inducing the immune system to eradicate cancers and viral infections in mice. We have defined human DC subsets and related their functional capacities to the mouse DC subsets. We will now identify the human DC subsets involved in the induction of cancer and viral immune responses and use this information to develop clinical therapeutic cancer vaccination trials.
This Program Grant has three investigators, Professor Denis Moss, Dr Rajiv Khanna and Dr Scott Burrows, each of whom has collaborated on two previous Program Grants. The group is well known in the area of herpesvirus immunology and have published numerous scientific papers in leading medical journals. This program grant focuses on two human herpesviruses. The first is called Epstein-Barr virus which causes glandular fever and is associated with arange of human cancers. The second virus is human ....This Program Grant has three investigators, Professor Denis Moss, Dr Rajiv Khanna and Dr Scott Burrows, each of whom has collaborated on two previous Program Grants. The group is well known in the area of herpesvirus immunology and have published numerous scientific papers in leading medical journals. This program grant focuses on two human herpesviruses. The first is called Epstein-Barr virus which causes glandular fever and is associated with arange of human cancers. The second virus is human cytomegalovirus which can cause birth defects and problems in transplant patients. In this program we are investigating how the body�s immune system controls these viruses to exploit this information to develop new treatments.Read moreRead less
Melanoma is a devastating disease. We are investigating new ways to treat and cure this form of cancer. Specifically, we are identifying how the body’s immune system interacts with melanoma and exploring new ways to use one’s own immune cells to destroy the cancer. This is achieved by understanding the interplay between various immune cells during melanoma and current therapies. This knowledge allows us to manipulate the immune cells providing better treatment.
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
Host-virus Interactions That Define The Outcome Of Anti-viral T Cell Responses: Relevance To Viral Persistence
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Infection with human cytomegalovirus (hCMV) is normally resolved without symptomatic evidence of infection. However, severe hCMV disease can occur in immunocompromised patients in which the manifestations of disease include chorioretinitis, interstitial pneumonia and hepatitis. In immunologically immature children, congenital infection results in cytomegalic inclusion disease (CID). CID in infants causes severe neurological sequelae resulting in mental retardation, deafness and blindness. Vaccin ....Infection with human cytomegalovirus (hCMV) is normally resolved without symptomatic evidence of infection. However, severe hCMV disease can occur in immunocompromised patients in which the manifestations of disease include chorioretinitis, interstitial pneumonia and hepatitis. In immunologically immature children, congenital infection results in cytomegalic inclusion disease (CID). CID in infants causes severe neurological sequelae resulting in mental retardation, deafness and blindness. Vaccination against hCMV induced cytomegalic inclusion disease has been designated Level I (most favourable) due to the prediction that it could save lives and prevent life-long disability. Given the essential nature of CD8 T cells in CMV control and the high prevalence of CMV in society, it will be crucial to develop a vaccine capable of eliciting an efficacious T cell response which develops lasting memory. We hypothesise that mCMV has evolved mechanisms for generating an appropriate T cell response involved in viral control and the establishment of a persistent infection. The central aim of the work in the current proposal is to investigate the cellular and viral mechanisms involved in the generation of cytomegalovirus specific T cells. The proposed studies will improve our understanding of the generation of anti-viral T cell responses and hence will be relevent to further our understanding of the role of T cells in human infection. More importantly the results will provide critical insights into the rational design of suitable antiviral drugs and vaccines.Read moreRead less
The human immune system comprises many different types of cells that can detect foreign molecules. My research will lead the way to understanding some of the most abundant, yet least well understood, cells within this system, collectively known as 'unconventional T cells'. This knowledge is essential to optimally and efficiently manipulate the immune system in health and disease.