Susan G Komen  
I've Been Diagnosed With Breast Cancer Someone I Know Was Diagnosed Share Your Story Join Us And Stay Informed Donate To End Breast Cancer
    Home > Research & Grants > Grants Program > Research Grants > Research Grants Awarded > Abstract

    Research Grants Awarded

    Developing Anti-Breast Cancer Therapies Based on G3BP

    Study Section:
    Tumor Cell Biology III

    Scientific Abstract:
    This project focuses on the G3BPs which are proteins implicated in cell cycle progression and tumour biology (Irvine etal. 2004) . Our interest is focussed on the role of G3BPs in breast cancer progression ( French etal. 2002) . The overall goal of the project is to examine ways of exploiting G3BP2 to develop anti-breast cancer therapeutics and to progress our current technology in breast cancer immunotherapy (Nestle etal. 2001) . The scientific aims of this project are: 1. To determine the correlation of G3BP2 expression in human breast cancers with those of other diagnostic cancer markers 2. To explore the role of G3BPs in cancer progression by examining its biological roles 3. To validate G3BP2 as a breast cancer Tumour Associated Antigen (TAA) for targeting immunotherapy Model We propose that G3BP2 is required by breast cancer cells to facilitate the tumour’s proliferation and progression. An immune response against G3BP2 would destroy the cancer by a specific CTL response to cells expressing the TAA. Techniques The validity of our model will be tested by addressing the aims of the projects using the following techniques: 1. To correlate the expression of G3BPs and other known breast cancer biomarkers in human breast cancer sections. This includes assessing sub-cellular localisation of the markers and correlation with clinical databases to determine the aggressiveness of the tumour. 2. Studying the biological role of G3BP by exploring its activity in oncogenic transcript processing. These studies are directed at determining if G3BPs are regulating cell cycle or tumour progression by regulating the expression oncogenic transcripts ( ie. c-myc ). 3. The project also describes the use of in vivo , biochemical and tumour-immunology techniques to assess G3BPs as valid targets for anti-breast cancer therapies or as Tumour Associated Antigens (TAA). This will be achieved by use of isolated human Dendritic cells and their activation by G3BP2-specific peptides or RNA loading. These cells will be used to activate naive T-lymphocytes to cytotoxic T-lymphocytes. Their activation will be assessed by elispot and chromium release assays. references French, J., Stirling, R., Walsh, M., and Kennedy, H.D. (2002) Histochemical Journal 34 : 223-231 Irvine, K., Stirling, R., Hume, D., and Kennedy, D. (2004). Int J Dev Biol 48 : 1065-1077 Nestle, F.O., Banchereau, J., and Hart, D. (2001). Nat Med 7 : 761-765

    Lay Abstract:
    Immunotherapy is a treatment for use in patients that relies on their own immune response to destroy a tumor. In many cases the body does not naturally raise an immune response against cancers because the tumor is not recognized as foreign and therefore left to grow uncontrolled. In our therapy, we activate the patient’s immune response by collecting white blood cells from a patient and “train” them to recognize the breast tumor. The white blood cells are then put back into the patient to elicit an immune response against the cancer. We have identified a protein, called G3BP2, which is over-expressed in many human breast cancers, and therefore can be used as a diagnostic and a target for immunotherapy. We aim to re-validate our data by correlating the expression of G3BP2 with other established diagnostic markers so that we can confidently present our data to clinicians in a fashion that they will accept the process we are proposing for clinical trials. We will also continue our work into defining the biological role of G3BP2, this work is designed to expand our knowledge of how G3BP2 may assist in the growth of tumors. Once we have established this role we can determine how to improve our current methods or discover other potential targets for anti-breast cancer therapies. Our experimental process will also focus on defining the optimum mechanisms for the delivery of our therapy once we have defined G3BP2 as a tumor associated antigen. Our goal is to enter clinical trials within the next 18 months with this procedure.