Her-2/neu-Crosreactive Analogs as Targets for 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 Her-2/neu protein is found in more than 35% of all breast cancers. Because Her-2/neu expression has been associated with metastatic disease, poor prognosis and low survival, this protein represents an excellent target for immunotherapy. Her-2/neu is a protein that is normally found in the body - a self protein. The immune system normally does not attack the body's own tissues or proteins. Therefore attempts to develop vaccines targeting the Her-2/neu are often disappointing because the immune responses against Her-2/neu are very weak and ineffective for tumor elimination or controlling tumor growth. The critical question is how to identify a system whereby immunization is able to stimulate an immune response capable of destroying effective Her-2/neu tumors.
 
 
 
 
 
 
 
 Vaccination strategies aimed at stimulating an immune response against Her-2/neu tumors utilizing the Her-2/neu protein have essentially failed. Therefore, we designed a strategy to identify a series of small molecules (crossreactive peptides) that mimic or resemble the Her-2/neu protein. We have already identified several crossreactive peptides. More importantly, since these crossreactive peptides are not self-proteins they are able to induce an immune response in which killer T cells (T cells are part of the immune system that help to clear out infections and malignancies such as cancer) effectively recognize Her-2/neu positive tumors. As such, these crossreactive peptides represent the potential for developing an effective vaccine against Her-2/neu tumors. Our objective is to develop a vaccine strategy with the use of the crossreactive peptides to induce strong immune responses that will effectively recognize Her-2/neu tumors and eliminate them.
 
 
 
 
 
 
 
 The efficiency of peptide vaccination relies on the incorporation of effective adjuvants. Adjuvants are molecules that stimulate and enhance immune responses. Therefore, the identification of safe and effective adjuvants is crucial for the development of effective peptide vaccines. In these studies, we will test two new adjuvants to evaluate which one promotes the most efficient immune response. We will use a mouse tumor model that we have established to test whether vaccination with a mix of adjuvant and crossreactive peptides induces an antitumor response in vivo. We will inject Her-2/neu positive tumors into mice which will then be vaccinated with a mixture of the adjuvant/crossreactive peptides and evaluated for tumor protection. In addition, we will test whether human anti-Her-2/neu-T cells will recognize the crossreactive peptides and analyze whether human T cells directed against the crossreactive peptides will kill Her-2/neu positive tumors. These experiments will demonstrate the potential of the crossreactive peptides to target Her-2/neu in the human setting.
 
 
 
 
 
 
 
 Currently there are no effective vaccines for the treatment of Her-2/neu breast tumors. We have used a new methodology to identify crossreactive peptides that can mimic or resemble the Her-2/neu protein. More importantly, these crossreactive peptides can induce an immune response (T cells) that effectively recognizes Her-2/neu positive breast tumors. The critical question is whether these crossreactive peptides serve as cancer vaccines. It is important to note, that these crossreactive peptides can be used in humans for the treatment of breast cancer. Moreover, the mouse tumor model that we have developed, reflect the closest scenario to the human setting .As such, the testing of the vaccination strategy with the crossreactive peptides in this mouse model will be of important clinical value because the information gained from these studies could form the basis for subsequent clinical studies. The analysis of the human-T cells will validate the use of the crossreactive peptides as tools for the treatment of Her-2/neu positive tumors.