Production Of Chimeric Monoclonal Antibodies To Pim1, A Novel Therapeutic Target For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$188,850.00
Summary
Almost one in six men will develop prostate cancer during his lifetime. Every year, around 10,000 Australian men are diagnosed and more than 2,500 die of the disease, making prostate cancer the second largest cause of male cancer deaths after lung cancer. The research progress made on prostate cancer over the past 10 years has been encouraging. However the five-year survival rate remains low. There is a vital need to develop new methods to treat this disease. An exciting principle has emerged re ....Almost one in six men will develop prostate cancer during his lifetime. Every year, around 10,000 Australian men are diagnosed and more than 2,500 die of the disease, making prostate cancer the second largest cause of male cancer deaths after lung cancer. The research progress made on prostate cancer over the past 10 years has been encouraging. However the five-year survival rate remains low. There is a vital need to develop new methods to treat this disease. An exciting principle has emerged recently with the use of monoclonal antibodies (Mabs) such as Herceptin (a humanised anti-HER2 Mab), which is now being widely used to treat breast cancer. We produced 2 Mabs to Pim1, which significantly inhibited prostate cancer cell growth in mouse prostate cancer model. Pim1 is a novel oncoprotein, a biomarker for the treatment of prostate cancer as it overexpresses in more than 90% of prostate cancer, but not or less expressed in normal prostate, demonstrated by genearrays and immunohistochemical staining. Pim1 plays an important role in cell survival, proliferation and metastasis. Pim1 is a novel target, and the anti-Pim1 Mabs may be of value for the cancer therapy in humans. However, the murine Mab can not be repeatedly used in human because human would produce anti-mouse antibody response, and the murine Mab would be rapidly removed from circulation, which will greatly limit the therapeutic potential of the Mabs. Fortunately, the problem can be overcome by the use of hybrid chimeric antibodies. In this study, we are going to use chimeric technology to humanise the anti-Pim1 Mab and test them in vitro and in mouse model for the preclinical studies. We have had patent to protect our finding, and we are confident to produce mouse-human chimeric Mab for the future clinical trial as we have proper knowledge, techniques. We are also optimic for the future clinical trial as we have the experiences on commercialisation.Read moreRead less
We seek to understand how white blood cells detect and destroy disease, and how molecules of the immune system punch holes in diseased cells. We wish to learn how cancer can sometimes evade the immune system. Our work will also find out how some common treatments for cancer, like chemotherapy, can be used to boost the immune system and eliminate tumours. Through knowledge gained from these studies, we aim to develop new therapies that can help patients with devastating diseases like cancer.
Investigating The Dynamic Interactions Between Immune And Cancer Cells Using Two-photon Intravital Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therap ....Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therapeutic approaches.Read moreRead less
This project will investigate a new class of targeted drugs called Smac-mimetics. These drugs are proving extremely effective in promoting the death of cancer cells. Here, we aim to better understand how Smac-mimetics work as a cancer therapeutic and how they promote immune responses to cancer. This will enable us to identify combination therapies that elicit both death of the cancer cell and stimulate the immune system to promote tumour clearance.
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.
This Program team will discover new things about immunity to cancer and virus infection and translate the information into novel therapies in patients with blood or solid cancers. The approaches will include new cellular or antibody therapies, alone or in combination. We will determine new predictive biomarkers to better select patients for therapy. We will overcome treatment resistance, improve the safety of combination therapies, and determine their best scheduling and dosing.
This application will increase the impact of cancer immunotherapy on disease prevention and treatment, by developing new targets and novel combination immunotherapies. Outcomes will include an improved understanding of the immune reaction with cancer and more effective strategies to prevent cancer spread and safely target and eradicate a larger proportion of established and advanced malignant disease.
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.
My goal is to boost the immune system against cancer to develop new therapies. I aim to do this by genetically engineering the immune system and using drugs to help strengthen white blood cells of the immune system. Tumors can actively fight immunity by producing suppressive molecules. I am seeking to identify and understand these molecules in order to block them and help the immune system fight cancer. Using this knowledge, I aim to start new clinical trials for cancer.
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