Vascular Targeting Therapy 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: Women with high risk breast cancer still succumb to their disease despite existing programs of adjuvant chemotherapy and hormonal therapy. Thus, new approaches for adjuvant therapy are needed. Increased expression of the Her-2-Neu oncogene correlates with recurrence, metastasis and resistance to adjuvant therapy. The immune response is tolerant of self-antigens like Her-2-Neu, since they have been present on epithelial cells since birth. Our laboratory has developed a vaccine strategy which can target markers unique to tumor vasculature as well as to Her-2-Neu vaccine, which can suppress the growth of breast cancer cells.
 
 
 
 
 
 
 
 The central hypothesis of the proposed research is that targeting the immune response directly to the blood vessels which supply the breast cancer will reduce the rate of recurrence of breast cancer after surgery. Our laboratory has developed a vaccine strategy that has been shown to induce an immune response to the Her-2-Neu receptor even in older test animals (which, like older humans, usually have a weakened immune response to vaccine). Our lab has now shown for the first time that it is possible to suppress the growth of breast cancer by directing the immune response against the blood vessels in breast cancer, a novel and powerful therapeutic strategy that could ultimately reduce the loss of life due to breast cancer.
 
 
 
 
 
 
 
 Our new vaccine is designed to trick the immune system into responding as if a viral infection is occurring. The viral infection is the strongest stimulus for activating the immune response. In this instance, the virus is engineered so that it is covered by markers (antigens) for the blood vessels of breast cancer tissue and by Her-2-Neu. We propose to test if a combined vaccine against the tumor blood vessels and breast cancer cells can prevent the development of breast cancer in a mouse which is genetically engineered for spontaneous development of breast cancer. In this model, breast cancer takes a long time to develop, just as in human beings.
 
 
 
 
 
 
 
 Be believe that our approach has novel elements that may allow success, despite the difficulties in mounting an effective immune response against breast cancer. The first innovative aspect is the development of an immune response against the blood vessels feeding the breast cancer tissue. The second novel aspect of this strategy is to combine the vaccine against the blood vessels of the tumor tissue with a vaccine against the breast cancer cells themselves. The third novel aspect of this approach is to combine these vaccine approaches with conventional adjuvant chemotherapy. Our laboratory has shown that delivery of chemotherapy during the vaccination process actually enhances the immune response induced by the vaccines. If this strategy were introduced into established programs of adjuvant chemotherapy, the success rate after surgery could go up, without any added toxicity.