The cancer preventive modality under study is a vaccine designed to elicit circulating antibodies that selectively target and neutralize insulin-like growth factor 1 (IGF-1) in the body. The underlying rationale is that many cancers will be far less likely to arise, develop, spread or recur in the absence of the stimulatory signals provided by this potent growth factor. IGF-1 is a small polypeptide hormone that plays a significant role in carcinogenesis due to its powerful mitogenic, hypertrophic and anti-apoptotic activities. In fact, many cancers over express the IGF-1 receptor which mediates its intracellular proliferative signaling. Moreover, epidemiological studies have linked high IGF-1 levels in the blood to several cancers including colorectal, prostate, uterine, bladder, ovarian and breast cancer. The Physicians'Health Study, for example, has indicated a strong association between circulating IGF-1 levels and the subsequent occurrence of prostate cancer. While IGF-1 is essential throughout embryogenesis and for spurts of statural growth during childhood, its necessity in adult life is much less compelling. Low levels of circulating IGF-I retard the progression and metastatic potential of a number of cancers. I have therefore developed a simple and safe vaccination procedure for inducing specific anti-IGF-1 antibodies. Those endogenous antibodies circulate in the blood and constitute a continuously present therapeutic for suppressing the stimulatory activity of IGF-1 in the body. The antibody-sequestered IGF-1 will be trapped in the blood stream and rendered incapable for interaction with receptors on cancer cells. To circumvent safety issues, vaccination would be initiated in early adult life when IGF-1 is no longer needed for growth and vital functions. Indeed, this immunotherapy and its beneficial effect could be maintained indefinitely via periodic booster injections. Thus, by continuously neutralizing the proliferation and survival benefits that IGF-1 provides to cancer cells, this IGF-1 vaccine approach would provide long-term prevention of cancer initiation, progression and recurrence. The cancer preventive action of these vaccines will be tested in several spontaneous tumor mouse strains.
The objective of this project is to develop a safe and simple cancer prevention vaccine that will delay or stop the development of that dreaded disease. The insulin-like growth factor 1 vaccine is designed to deprive cancerous and precancerous cells of this crucial growth factor which they need to survive.
