Insulin-like Growth Factor 1 Vaccine for Cancer Prevention

用于预防癌症的胰岛素样生长因子 1 疫苗

基本信息

批准号：
7589329
负责人：
VICTOR A RASO
金额：
$ 10.15万
依托单位：
BOSTON BIOMEDICAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-22 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7589329
关键词：
Active Immunization Adult Animal Cancer Model Animal Model Animals Antibodies Antibody Formation Antibody Therapy Antigens Apoptotic Applications Grants Binding Biochemical Pathway Biological Biological Assay Biological Models Bladder Blood Caloric Restriction Childhood Colorectal Development Embryonic Development Endocrine Enzyme-Linked Immunosorbent Assay Epidemiologic Studies Epitopes Facility Construction Funding Category Gene Mutation Glucose Growth Growth Factor Health Human Immune Sera Immunotherapy Injection of therapeutic agent Insulin Insulin-Like Growth Factor I Insulin-Like-Growth Factor I Receptor Keyhole Limpet Hemocyanin Life Link Longevity Malignant Neoplasms Malignant neoplasm of prostate Measures Mediating Modality Monitor Mouse Strains Mus Mutation Numbers Ovarian Pathway interactions Peptides Physicians Physiological Play Polypeptide Hormones Prevention strategy Preventive Procedures Prostate Recurrence Research Risk Role Route Safety Serum Signal Transduction Specificity Stream Supplementation Testing Therapeutic Therapeutic Agents Time Treatment Protocols Vaccinated Vaccination Vaccine Design Vaccines base cancer cell cancer prevention cancer risk carcinogenesis cross reactivity design dietary restriction malignant breast neoplasm mouse model novel prevent prototype receptor research study sound tumor

项目摘要

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.

描述（由申请人提供）：正在研究的癌症预防方式是一种疫苗，旨在引发循环抗体，选择性地靶向并中和体内的胰岛素样生长因子 1 (IGF-1)。其基本原理是，如果没有这种有效的生长因子提供的刺激信号，许多癌症发生、发展、扩散或复发的可能性就会大大降低。 IGF-1是一种小多肽激素，由于其强大的促有丝分裂、肥大和抗凋亡活性，在致癌作用中发挥着重要作用。事实上，许多癌症过度表达 IGF-1 受体，该受体介导其细胞内增殖信号传导。此外，流行病学研究已将血液中高 IGF-1 水平与多种癌症联系起来，包括结直肠癌、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 IGF-1 水平与随后发生的前列腺癌之间存在密切关联。虽然 IGF-1 在整个胚胎发生和儿童时期的体格生长突增过程中至关重要，但它在成年生活中的必要性却远没有那么引人注目。循环中低水平的 IGF-I 可延缓多种癌症的进展和转移潜力。因此，我开发了一种简单且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，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。为了规避安全问题，当生长和生命功能不再需要 IGF-1 时，将在成年早期开始接种疫苗。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 为癌细胞提供的增殖和生存益处，这种 IGF-1 疫苗方法将提供对癌症发生、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性肿瘤小鼠品系中进行测试。