Cancer Vaccines for Hormone/Growth Factor Immune Deprivation:A Feasible Approach for Cancer Treatment

Abstract

One of the older and most validated cancer treatments is endocrine therapy. Some tumors are dependent on hormone stimulation for growth, and therefore therapeutic interventions aiming to deprive the cells of the hormone are feasible and have been successful. Tumor growth also depends in some cases on growth factors, so that the concept of hormone-dependence can be extended to growth factors deprivation. Hormone deprivation has been therapeutically achieved up to now by surgical, radiation and chemical means. However, the immune system usually can be manipulated to recognize hormones and growth factors, and in fact some autoimmune diseases exists involving autoantibodies against hormones. The idea of inducing a deprivation of hormones and growth factors by active immunizations is appealing, and initial evidence about the feasibility of this approach is starting to appear in the literature. Clinical trials have been initiated using immunization with human chorionic gonadotrophin (hCG), gastrin, luteinizing hormone releasing hormone (LHRH) / gonadotropin releasing hormone (GnRH) and epidermal growth factor (EGF). Preliminary data already show that antibody titers can be elicited, which results in a decrease in the concentration of a given hormone or growth factor. Both the antibody titers and the decrease in the hormone level are related to survival. This immunological approach for hormone and growth factor deprivation creates the possibility of chronic management of advanced cancer patients.

A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non–Small Cell Lung Cancer Patients

“…CIMAvax-EGF is built on the induction of a specific immune response, aiming to sequester EGF, a molecular driver of cancer cell proliferation (11)(12)(13)(14)(15). Its mechanism of action is based on the "hormone deprivation theory" that has proven to be effective for sexual hormones-dependent tumors (10). The rationale of CIMAvax-EGF is based on the finding that EGF concentration is higher in NSCLC patients than in normal donors.…”

“…The EGF-based cancer vaccine CIMAvax-EGF is an active immunotherapy, intended to prevent binding of the endogenous EGF to the receptors, by inducing anti-EGF antibodies that clear the growth factor from circulation (10). CIMAvax-EGF is composed by human recombinant EGF coupled to a carrier protein, recombinant P64.…”

Strong humoral response elicited by a DNA vaccine targeting gastrin-releasing peptide with optimized adjuvants inhibits murine prostate carcinoma growth in vivo

“…The strategy of exploiting anti-EGF autoantibodies to block the EGF/EGFR autocrine loop reduces the growth rate of EGF-dependent tumors, which can also support the function of anti-GRP autoantibodies in reducing the growth rate of GRP-dependent tumors. Both GRP and EGF deprivation therapy can be classified into therapeutic interventions aiming to deprive cancer cells of their required hormone or growth factor, as reviewed in Gonzalez & Lage (2007). Clinical trials have been initiated using immunization with human chorionic gonadotrophin, gastrin, LHRH/ GnRH, and EGF.…”

Vaccination with a potent DNA vaccine targeting B-cell epitopes of hGRP induces prophylactic and therapeutic antitumor activity in vivo

“…Furthermore, cultured RM-1 cells exposed to GRPspecific Abs results in inhibition of cell growth rate as well as apoptotic cell death. This strategy of exploiting GRP auto-Abs to block the GRP/GRPR autocrine or paracrine loop reduces the growth rate of GRP-dependent tumors, and can be classified into therapeutic interventions aiming to deprive cancer cells of their dependent hormone or growth factor, as reviewed by Gonzalez et al 11 These vaccines have been designed with a different purpose: to activate an Ab immune response against self-hormones and/or growth factors that participate in the stimulation of tumor growth. Clinical trials have been initiated using immunization with human chorionic gonadotrophin, gastrin, gonadotropinreleasing hormone and epidermal growth factor.…”

“…The idea of inducing a deprivation of hormones and growth factors by active immunizations is appealing, and initial evidence regarding the feasibility of this approach for cancer treatment is starting to appear in the literature. 11 This immunological deprivation approach targeting GRP, which can act as growth factor in many types of cancers, may also create the possibility of chronic management for GRP-dependent cancer treatment.…”