Insulin-like Growth Factor 1 Vaccine for Cancer Prevention

描述（由申请人提供）： 正在研究的癌症预防模式是一种疫苗，旨在引发循环抗体，选择性地靶向和中和体内的胰岛素样生长因子1（IGF-1）。其基本原理是，如果没有这种强效生长因子提供的刺激信号，许多癌症的发生、发展、扩散或复发的可能性要小得多。IGF-1是一种小的多肽激素，由于其强大的促有丝分裂、肥大和抗凋亡活性，其在癌发生中起重要作用。事实上，许多癌症过度表达介导其细胞内增殖信号传导的IGF-1受体。此外，流行病学研究已经将血液中的高IGF-1水平与几种癌症联系起来，包括结肠直肠癌、前列腺癌、子宫癌、膀胱癌、卵巢癌和乳腺癌。例如，医生健康研究表明，循环中的IGF-1水平与随后发生的前列腺癌之间存在很强的关联。虽然IGF-1在整个胚胎发育过程中以及儿童时期的体格生长中至关重要，但其在成年生活中的必要性却不那么引人注目。低水平的循环IGF-I延缓许多癌症的进展和转移潜力。因此，我开发了一种简单而安全的疫苗接种程序，用于诱导特异性抗IGF-1抗体。这些内源性抗体在血液中循环，并构成持续存在的治疗剂，用于抑制体内IGF-1的刺激活性。抗体隔离的IGF-1将被困在血流中，无法与癌细胞上的受体相互作用。为了避免安全性问题，疫苗接种将在成年早期开始，那时生长和重要功能不再需要IGF-1。事实上，这种免疫疗法及其有益效果可以通过定期加强注射无限期地维持。因此，通过持续中和IGF-1提供给癌细胞的增殖和存活益处，这种IGF-1疫苗方法将提供对癌症起始、进展和复发的长期预防。这些疫苗的癌症预防作用将在几种自发肿瘤小鼠品系中进行测试。

DESCRIPTION (provided by applicant): 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.