Cryptic Peptides-Based Vaccines for Breast Tumor Treatment
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: Her-2/neu protein is found to be in more than 35% of all breast cancers. Her-2/neu expression has been associated with metastatic disease, poor prognosis and low survival, as such this protein represents an excellent target for immunotherapy. The immune system normally does not attack the body’s own tissues or proteins. Considering that Her-2/neu is a protein found naturally in the body (a self-protein), 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 growth control. The challenge is to identify a system where vaccines can induce strong immune responses against Her-2/neu to cause tumor rejection.
 
 
 
 
 
 
 
 Our goal is develop a vaccine strategy that will induce the generation of potent immune responses capable of eliminating Her-2/neu positive tumors. Our strategy is to identify a series of small molecules (cryptic peptides) that mimic or resemble the Her-2/neu. Since these small molecules are not self-proteins we will be able to induce strong immune responses that will recognize Her-2/neu positive tumors and eliminate them. We have already identified some small molecules that effectively recognize Her-2/neu tumors. Our objective is to test these small molecules (cryptic peptides) as cancer vaccines.
 
 
 
 
 
 
 
 We used a new chemical methodology called positional scanning synthetic peptide combinatorial library (PS-SCL) to identify small molecules recognize by T cells (T cells are part of the immune system that help to clear out infections and malignancies such cancer). By screening the chemical libraries of small molecules (peptides) with T cells specific for Her-2/neu that we have developed previously, we were able to identify some small molecules recognized by these T cells. We used a mouse model to test whether these small molecules induce a T cell response in vivo. Our results demonstrate that these small molecules induce a T cell response and these T cells kill Her-2/neu breast tumors with high efficiency. These results demonstrated that these small molecules are effective inducers of immune responses. We will use our mouse tumor model to test these small molecules as cancer vaccines. We will inoculate mice with tumor cells, vaccinate them with the small molecules and then evaluated the vaccine for tumor protection.
 
 
 
 
 
 
 
 Currently there are no effective vaccines for the treatment of Her-2/neu breast tumors. The studies proposed here will allow us to test for the first time if the small molecules (cryptic peptides) we have identified are good candidates for cancer vaccines. Importantly, these small molecules can be used in humans for the treatment of breast cancer. As such, these peptides could be of great clinical value and the information gain from these studies could form the basis for future studies in the clinic.