Generating Tumour-Specific Dendritic Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such dang ....Therapies using the immune system are showing promise for cancer treatment, particularly for melanoma, but complete durable responses are few and improvements are needed. We believe that such immunotherapies, in their current form, fail to sufficiently mimic a natural immune reaction to disease, and therefore fall short of effectively controling cancer. In particular, an alarm (danger signal) is not produced within tumour as it would be when the body is challenged by infectious agents. Such danger signals are critical for the immune system to respond effectively and for white blood cells of the immune system to find their way to the disease organism and eliminate it. The strongest danger signals are produced by a type of white blood cell known as a dendritic cell (DC). These cells detect infectious agents and produce biochemical alarm molecules that alert the entire immune system to the danger resulting in powerful action against the disease. However, tumours are really just a part of our own body and no danger signal is produced. It is our aim to use genetic modification to make DC see tumours as a threat and produce danger signals. These gene-modified DC either alone, or in combination with other immunotherapies, may lead to destruction of tumours.Read moreRead less
Targeting Human Dendritic Cells In A Multiple Myeloma Humanized NOD/SCID Model
Funder
National Health and Medical Research Council
Funding Amount
$425,696.00
Summary
Adoptively transferred dendritic cells (DC) loaded with tumor associated antigen (TAA) have been shown to induce anti-tumor immunity in animal models; however, their therapeutic efficacy in cancer patients has not been established. Protective immunity has failed in the tumor-bearing host and the ability of human DC to induce anti-tumor responses in the abnormal environment of the cancer patient requires further investigation. Due to the limited capacity to investigate the DC-tumor interaction in ....Adoptively transferred dendritic cells (DC) loaded with tumor associated antigen (TAA) have been shown to induce anti-tumor immunity in animal models; however, their therapeutic efficacy in cancer patients has not been established. Protective immunity has failed in the tumor-bearing host and the ability of human DC to induce anti-tumor responses in the abnormal environment of the cancer patient requires further investigation. Due to the limited capacity to investigate the DC-tumor interaction in patients, humanized animal models containing human DC and tumor provide an opportunity to obtain important new information. We propose to develop multiple myeloma (MM) as a human tumor in our humanized (hu)NOD-SCID model containing human DC, and to use this in vivo MM-huNOD-SCID model to restore immunity by correcting the human DC-tumor interaction.This knowledge will act as a fast track to select and design a new (simplified) DC-based immunotherapy to treat cancer patients and will be translated directly into our MM clinical trials program, potentially by targeting human DC based on CD205 recognition.Read moreRead less
Strategies To Enhance CD4 T Cell-mediated Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
The immune system is capable of controlling cancer, but frequently does not do so. In this project we will study two factors that compromise anti-cancer immune responses: regulatory T cells, which suppress immune responses, and tolerogenic dendritic cells, which subvert potentially beneficial responses to tumours. By manipulating these factors, we hope to enhance the effectiveness of the immune response against cancer.
A NOVEL APPROACH FOR TARGETING DNA TO DENDRITIC CELLS IN VIVO FOR VACCINE DEVELOPMENT AND CANCER IMMUNOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$430,250.00
Summary
The use of genetic material, known as DNA, as a vaccine, has been a relatively new advance in vaccination technology with potential for combating many infectious diseases and cancers. The use of DNA has the advantage that it can be easily manipulated to develop new vaccines that have the desired preventative and-or immunotherapeutic effect. For optimal effect, however, the DNA to be used as a vaccine needs to be targeted to specific cell types in the body. Evidence suggests that a minor populati ....The use of genetic material, known as DNA, as a vaccine, has been a relatively new advance in vaccination technology with potential for combating many infectious diseases and cancers. The use of DNA has the advantage that it can be easily manipulated to develop new vaccines that have the desired preventative and-or immunotherapeutic effect. For optimal effect, however, the DNA to be used as a vaccine needs to be targeted to specific cell types in the body. Evidence suggests that a minor population of cells known as dendritic cells, which are present in blood and other tissues, play an important role in eliciting the effects of DNA vaccines. However, current methods for delivering DNA to these cells often lack selectivity in delivery, and-or use viruses to deliver the DNA. This can pose the risk of allergic type reactions and-or possibly cause tumours. The use of small membranous vesicles known as liposomes, made of phospholipids, has recently attracted considerable interest as DNA delivery vehicles, since these are considered safe, and have the potential to deliver large quantities of DNA. Although DNA can easily be packaged inside liposomes, it is has not been easy to target the liposomes and their contents (eg. encapsulated DNA) to specific cells (such as dendritic cells) within the body. We have recently produced a novel chelator lipid molecule which can be used to conveniently attach onto the liposome surface specific targeting molecules, such as engineered forms of antibody fragments, that can target or steer the liposomes together with their payload (eg. the DNA), directly to dendritic cells. This project will test the potential for using such targeted liposomes as DNA vaccines by examining whether liposomes containing DNA for a model antigen can be used in vaccinations to inhibit the growth and metastasis of a highly metastatic tumour (melanoma) in mice.Read moreRead less