Abstract A11: Insulin-like growth factor vaccine for the global prevention of adult cancers

The purpose of this study is to develop a single vaccine that will prevent a variety of different cancers. It functions by reducing the supply of insulin-like growth factor (IGF) required for carcinogenesis. A safe, widely applicable preemptive treatment can greatly curtail cancer deaths. Primary prevention precludes the confounding problems associated with advanced cancer such as its resistance to treatment, its eventual recurrence and the progression to metastatic disease. This novel prevention strategy is based on studies of a small population of individuals in Ecuador who are cancer free their entire lifetime due to genetically low IGF levels. In contrast, 14% of their IGF-replete relatives succumbed to 20 different types of malignancy. That compelling human example of the benefit of reduced IGF activity suggests that the initiation or early progression of many cancers requires IGF. Thus, the objective is to develop protective vaccines to neutralize the multiple activities of IGF that promote oncogenesis. The ultimate goal is to vaccinate at risk adults and achieve the same protection from cancer experienced by the IGF-deficient Ecuadorians. The concept is predicated on the hypothesis that a lingering high level of IGF stimulation is superfluous after adolescence and, in later years, becomes detrimental to health. There are strong survival benefits for its simultaneous mitogenic, hypertrophic and antiapoptotic activities to operate during growth and development. Alas, there is no evolutionary pressure to develop a post-reproductive IGF shutoff mechanism. So, as science and medicine steadily extend the human lifespan, we find ourselves in the dilemma of having to accommodate a persistent pro-cancer hormone with little or no other purpose. This hypothesis fits with the age dependent increase of cancer incidence. Conventional and cutting-edge, nanofiber-based epitope vaccines have been produced to test this idea. They are designed to actively induce antibodies that either neutralize IGF directly or block a key enzyme that regulates IGF bioavailability. The continuous presence of such inhibitory antibodies would keep IGF activity at a constantly low level and thereby preemptively block the development of incipient cancers later in life. Antisera from mice immunized with those vaccines contained epitope-specific IgG antibodies that were reactive with recombinant IGF in ELISA studies. An ultrafiltration method was also used to demonstrate specific binding of recombinant 125I-IGF after incubation with undiluted antiserum versus non-immune control sera (conditions that mimic in vivo therapy). Exploratory tests indicated that the vaccine delayed the appearance of tumors in mice that develop sarcomas due to SV40 Tag expression. Safety is undeniably paramount for any new cancer prevention therapy and apprehension about targeting the ubiquitously expressed IGF is understandable. In terms of human health consequences however, the IGF-deficient Ecuadorians represent a worst-case scenario since they are severely depleted from birth onwards. Although very short due to their life-long IGF deficit, this cancer-free population is surprisingly healthy and long-lived (some >80 years old). Nevertheless, to further ensure safety the IGF-suppressive vaccines will be administered exclusively to fully grown and developed adults. Preemptive vaccination at 40-50 years old would be most effective since a majority of human malignancies occur beyond the age of 60 and because this postponement will circumvent impairment of normal growth or other juvenile functions. The prevention vaccines could be used; 1) for people with a genetic likelihood to develop familial cancer, 2) as an adjuvant following precancerous growth removal, 3) to inhibit relapse for patients in remission, and 4) as a general prophylactic to curtail sporadic, age-dependent cancers. Citation Format: Victor Raso. Insulin-like growth factor vaccine for the global prevention of adult cancers. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A11.