Antibody Fusion Proteins for the Therapy of Breast Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The management of residual disease is a central problem in breast cancer. Despite extensive efforts, relapse remains a critical and generally fatal problem in high-risk breast cancer patients. Conventional treatments such as chemotherapy are limited in their efficacy by various toxicities and by tumor resistance. Additional modalities that will achieve better results are needed. A variety of investigators have suggested transferring genes for molecules that stimulate the immune system into tumor cells to augment the immune response against them. Many of these strategies involve manipulation of tumor cells outside the patient, which is technically difficult to implement and does not target all tumor deposits. We propose an alternative approach in which molecules that stimulate the immune system can be selectively delivered to the tumor cells of a metastatic/residual nodule by a tumor specific antibody. It is anticipated that the molecules will engender a potent immune response against the targeted tumor.
 
 
 
 
 
 
 
 Using genetic engineering techniques, we have joined antibodies to molecules that are stimulators of the immune system producing "antibody fusion proteins". Over the last several years work in our laboratory has focused on producing antibody fusion proteins with novel biologic activities. We now propose to further explore the use of genetically engineered antibody fusion proteins as therapeutic agents specifically attempting to augment and potentiate the patient’s immune system against breast cancer. We will use antibodies specific for the breast cancer associated molecules her2/neu and CEA. Overexpression of her2/neu has been associated with poor prognosis making it especially promising for targeting residual disease in breast cancer. To these antibodies we will join either IL-2 or B7-1, both of which have been shown to be effective in increasing the immune response against tumors. We anticipate that the antibody will carry the immunostimulatory molecule to the site of the tumor where it will stimulate the human immune system to recognize and destroy the cancer cells, which otherwise might escape conventional treatment.
 
 
 
 
 
 
 
 The first generation of these fusion proteins has been made. The fusion proteins are of the expected size and carry out antibody related activities as well as the activity of the immuno-stimulator molecule that was joined to the antibody. The next step will be determining the properties of the fusion proteins in animals and their effectiveness in eliciting an anti-tumor response. We will test the effectiveness of the fusion proteins in eliminating established breast cancer using tumor models in mice. We have introduced the genes for her2/neu and CEA into mouse tumors so that we can investigate the efficacy of our treatment in immunocompetent mice. Using different tumor models, we and others have shown that antibody fusion proteins can have a superior protective effect due to specific stimulation of the immune response. We are now in an excellent position to determine if this approach can be extended to the treatment of minimal residual disease in breast cancer.
 
 
 
 
 
 
 
 The present studies represent a novel extension of previous reports and address the priority issue "Innovative Treatment Modalities" that can contribute significantly to reducing the cost of breast cancer in California.