Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer

Simms, Matthew; Scholfield, David; Jacobs, Elizabeth R.; Michaeli, D; Broome, P.; Humphreys, Jane; Bishop, M. C.

doi:10.1054/bjoc.2000.1315

Cited by 69 publications

(39 citation statements)

References 11 publications

(9 reference statements)

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“…Titers were only slightly increased in two stallions, while two other stallions responded with substantial antibody titers. Such a large variation in antibody responses after GnRH immunization is shown in the majority of the GnRHimmunization studies in which sexually mature subjects are involved (Chappel et al, 1980;Lincoln et al, 1982;Schanbacher et al, 1983;Grizzle et al, 1987;Simms et al, 2000;Malmgren et al, 2001). Several factors may affect the immunogenicity of the applied vaccines, such as the type and amount of antigen, the adjuvant, vaccination schedule and the species involved.…”

Section: Discussionmentioning

confidence: 99%

Effects of GnRH immunization in sexually mature pony stallions

Turkstra

Meer

Knaap³

et al. 2005

Animal Reproduction Science

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Immunization against gonadotrophin releasing hormone (GnRH) was studied as an alternative for the commonly used surgical castration in stallions. Two GnRH vaccines comprising non-mineral oil adjuvants were evaluated for their potential to induce high antibody titers directed against GnRH and subsequent effects on reproductive characteristics. Twelve sexually mature male hemicastrated Shetland ponies were assigned to three groups. Group 1 and 2 were injected with 1 mg peptide equivalent of G6k-GnRH-tandem-dimer conjugated to ovalbumin (OVA) in CoVaccine TM HT adjuvant (GnRH/CoVaccine) and in Carbopol (GnRH/Carbopol), respectively, and group 3 was injected with CoVaccine TM HT adjuvant without antigen (controls).After immunization no adverse effects were observed with respect to the injections sites or general health. Two weeks after the second vaccination antibody titers against GnRH increased rapidly in all animals of the GnRH/CoVaccine group, at the same time reducing serum testosterone levels maximally for the further duration of the experiment. In the GnRH/Carbopol group antibody responses and effects on testosterone levels were intermediate in two stallions and not apparent in the remaining stallions of this group. * Corresponding author. Tel.: +31 320 237212; fax: +31 320 238120.E-mail address: j.turkstra@pepscan.nl (J.A. Turkstra). J.A. Turkstra et al. / Animal Reproduction Science 86 (2005) 247-259Semen evaluation showed that from 2 weeks after the second immunization onwards, sperm motility was affected in all stallions treated with GnRH/CoVaccine and one stallion treated with GnRH/Carbopol. Seven weeks after the second immunization, no semen could be collected from two stallions, one of each group, due to suppressed libido. Histological examination of the testes, 15 weeks after the initial immunization, demonstrated reduction in seminiferous tubuli diameters in all stallions of the GnRH/CoVaccine group and one stallion of the GnRH/Carbopol group. Furthermore, spermatogenesis was extremely disorganized in these stallions, as indicated by absence of the lumen in the seminiferous tubules, the absence of spermatozoa and spermatids in the tubular cross-sections and the impossibility to determine the stage of the tubular cross-sections. Testis size was also substantially reduced in three out of four stallions treated with GnRH/CoVaccine.The results demonstrate that two immunizations with G6k-GnRH-tandem-dimer-OVA conjugate in a suitable adjuvant such as CoVaccine TM HT caused a rapid and complete reduction of serum testosterone levels in sexually mature stallions, subsequently leading to reduced sperm motility and affected testis function, while no adverse reactions were observed after immunizations.

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Section: Discussionmentioning

confidence: 99%

Effects of GnRH immunization in sexually mature pony stallions

Turkstra

Meer

Knaap³

et al. 2005

Animal Reproduction Science

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“…We did not specifically address the duration of the immune response, but various reports evidently show that immune responses raised against endogenous antigens are fully reversible (38)(39)(40)(41)(42). Long-term data with a peptide-based GnRH-targeting cancer vaccine for testosterone deprivation, also developed by us (43), showed that testosterone levels reappeared ∼30 wk later (43), showing that anti-GnRH immunity is indeed reversible.…”

Section: Discussionmentioning

confidence: 99%

Targeted vaccination against the bevacizumab binding site on VEGF using 3D-structured peptides elicits efficient antitumor activity

Wentink

Hackeng

Tabruyn

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Therapeutic targeting of the VEGF signaling axis by the VEGFneutralizing monoclonal antibody bevacizumab has clearly demonstrated clinical benefit in cancer patients. To improve this strategy using a polyclonal approach, we developed a vaccine targeting VEGF using 3D-structured peptides that mimic the bevacizumab binding site. An in-depth study on peptide optimization showed that the antigen's 3D structure is essential to achieve neutralizing antibody responses. Peptide 1 adopts a clear secondary, native-like structure, including the typical cysteine-knot fold, as evidenced by CD spectroscopy. Binding and competition studies with bevacizumab in ELISA and surface plasmon resonance analysis revealed that peptide 1 represents the complete bevacizumab binding site, including the hairpin loop (β5-turn-β6) and the structure-supporting β2-α2-β3 loop. Vaccination with peptide 1 elicited high titers of cross-reactive antibodies to VEGF, with potent neutralizing activity. Moreover, vaccination-induced antisera displayed strong angiostatic and tumor-growth-inhibiting properties in a preclinical mouse model for colorectal carcinoma, whereas antibodies raised with peptides exclusively encompassing the β5-turn-β6 loop (peptides 15 and 20) did not. Immunization with peptide 1 or 7 (murine analog of 1) in combination with the potent adjuvant raffinose fatty acid sulfate ester (RFASE) showed significant inhibition of tumor growth in the B16F10 murine melanoma model. Based on these data, we conclude that this vaccination technology, which is currently being investigated in a phase I clinical trial (NCT02237638), can potentially outperform currently applied anti-VEGF therapeutics.VEGF | angiogenesis | immunization | protein mimicry | peptide vaccines

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“…Suppression of testosterone via an anti-LHRH response leads to a reduction in dihydrotestosterone and indirectly controls prostatic hyperplasia. A related application for anti-LHRH vaccines in men is for treatment of prostatic cancer, and a number of phase I/II studies have shown some degree of efficacy in men with this tumor (168).…”

Section: Vaccines Against Reproductive Hormonesmentioning

confidence: 99%

Current Status of Veterinary Vaccines

et al. 2007

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SUMMARY The major goals of veterinary vaccines are to improve the health and welfare of companion animals, increase production of livestock in a cost-effective manner, and prevent animal-to-human transmission from both domestic animals and wildlife. These diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations, and naked DNA injections. The final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace or that will be used in the field to achieve desired outcomes. As detailed in this review, successful veterinary vaccines have been produced against viral, bacterial, protozoal, and multicellular pathogens, which in many ways have led the field in the application and adaptation of novel technologies. These veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies and preventing animal-to-human transmission of infectious diseases. The continued interaction between animals and human researchers and health professionals will be of major importance for adapting new technologies, providing animal models of disease, and confronting new and emerging infectious diseases.

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Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer

Cited by 69 publications

References 11 publications

Effects of GnRH immunization in sexually mature pony stallions

Effects of GnRH immunization in sexually mature pony stallions

Targeted vaccination against the bevacizumab binding site on VEGF using 3D-structured peptides elicits efficient antitumor activity

Current Status of Veterinary Vaccines

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