Receptor Antibody-Enhanced Chemotherapy 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: We now know that cancer arises as a result of a series of molecular alterations in normal cells including overexpression of growth factors that could facilitate uncontrolled cell growth. Insulin-like growth factor (IGF)-I and -II are growth factors. IGF-I is thought to play an important role in development after birth with the majority of circulating IGF-I coming from the liver. IGF-II, on the other hand, is assumed to be an important growth factor in fetal and newborn development. Abnormal overexpression of these IGFs in cancer has increasingly been recognized. It is known that IGF-I and -II are potent growth factors for a variety of cancer cells, including breast cancer cells. In addition, several lines of experimental evidence suggest that an increase in IGF-II expression is associated with malignant progression of breast cancer cells whereas a decrease of IGF-II expression results in growth inhibition of these cells. The growth effects of IGF-II and -I are mediated through the IGF-I receptor (IGFIR), that is, IGFs tell the cells to start growth by binding to IGFIR.
 
 
 
 
 
 
 
 Based on these observations, we have designed innovative experiments that interrupt IGFs/IGFIR growth signaling by introducing a "receptor antibody" that keeps IGFs from binding to IGFIR. Treatment of breast cancer cells with existing IGFIR-specific antibody (aIR-3) has been shown to reduce IGF-stimulated cell growth. Our anti-IGFIR antibody, IH7, is apparently even better at interrupting IGF/IGFIR signaling. This fact indicates that IH7 is a desirable candidate for testing the effect of receptor antibodies on cancer cell growth inhibition. Two versions of IH7 antibodies have been produced using "state of the art" bioengineering technologies. One form should be able to inhibit IGF actions from outside cells whereas the other should be able to inhibit IGFIR function inside cells. In addition, we plan to test this receptor antibody therapy in conjunction with chemotherapy for breast cancer in order to maximize its potential effect. We expect that the proposed "Receptor antibody-enhanced chemotherapy" would not only enhance sensitivity of cells with lots of IGFIR to chemotherapy, but also affect other cancer cells that don’t have as much IGFIR. It is hoped that the proposed study will lead to the development of new therapeutics for breast cancer treatment. The enhancement strategies for chemotherapy by anti-growth factor receptor antibodies are now believed to lead to new strategies for clinical interventions shown to inhibit IGF-stimulated cell growth.
 
 
 
 
 
 
 
 Antibody strategies to inhibit IGF-stimulated breast cancer cell growth have never been tested. Accomplishment of such antibody strategies would lay the foundation for the development of future breast cancer therapeutics utilizing chemo/immuno/gene therapy. Thus, this proposal will fit into one of the Priority Issues included in Cycle III, "Innovative Treatment Modalities".