Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat

Rovan, E.; Fiebiger, Eduard; Kalla, N.R.; Talwar, G.P.; Aulitzky, W.; Frick, J.

doi:10.1007/bf00922744

Cited by 26 publications

(13 citation statements)

References 14 publications

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“…Because the sequence of LHRH is conserved in all mammals, LHRH-based immunocontraceptives are candidates for use in the companion animal and livestock arenas. Here the concerns of behavioral modification are not of such overriding importance and the use of immunocontraception as an alternative to surgical castration has attracted a great deal of attention (5,(7)(8)(9)(10).…”

Section: Highly Immunogenic and Totally Synthetic Lipopeptides Asmentioning

confidence: 99%

Highly Immunogenic and Totally Synthetic Lipopeptides as Self-Adjuvanting Immunocontraceptive Vaccines

Zeng

Ghosh

Lau

et al. 2002

The Journal of Immunology

179

188

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In this study, we describe the synthesis of various lipopeptides based on the sequence of luteinizing hormone-releasing hormone (LHRH) and report on their abilities to induce Abs against this “self” hormone when inoculated into mice in the absence of additional adjuvant. The peptides consisted of a colinear CD4+ T helper cell epitope from the L chain of influenza virus hemagglutinin and LHRH, which has B cell epitopes but no T cell epitopes present in its sequence. Lipids were attached either at the N terminus or between the T cell epitope and LHRH, in the approximate center of the peptide. The lipopeptide constructs displayed different solubilities and immunological properties that depended not only on the lipid content but also on the position of attachment of the lipids. Some of these constructs were highly immunogenic, inducing high titers of Ab, which were capable of efficiently sterilizing female mice when administered in saline by s.c. or intranasal routes. The most effective vaccines were highly soluble, contained the dipalmitoyl-S-glyceryl cysteine moiety, and had this lipid attached at the center of the molecule. The relative ability of the lipopeptides to induce an Ab response in the absence of external adjuvant was reflected by their ability to up-regulate the surface expression of MHC class II molecules on immature dendritic cells. These results demonstrate that the composition and position within peptide vaccines of self-adjuvanting lipid groups can influence the ability to induce the maturation of dendritic cells and, in turn, the magnitude of the resulting Ab response.

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Section: Highly Immunogenic and Totally Synthetic Lipopeptides Asmentioning

confidence: 99%

Highly Immunogenic and Totally Synthetic Lipopeptides as Self-Adjuvanting Immunocontraceptive Vaccines

Zeng

Ghosh

Lau

et al. 2002

The Journal of Immunology

179

188

View full text Add to dashboard Cite

show abstract

“…An obvious application of the vaccine is in hormone-dependent cancers, as a cheap and convenient alternative to the LHRH agonists and antagonists. Immunization of rats with the LHRH vaccine causes a dramatic atrophy of the prostate of rats [1][2][3]. A marked reduction in the size of the prostate was also observed in monkeys [4].…”

Section: Introductionmentioning

confidence: 80%

“…Previous studies have shown that immunization against LHRH causes a marked atrophy of the rodent and monkey prostates [1][2][3][4]. The vaccine [7] generated antibodies that inactivate LHRH, with consequent downregulation of the pituitary-testis axis.…”

Section: Discussionmentioning

confidence: 99%

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Induction of early and bioeffective antibody response in rodents with the luteinizing hormone-releasing hormone vaccine given as a single dose in biodegradable microspheres along with alum

Diwan¹,

Dawar²,

Gp³

1998

Prostate

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“…An antibody-inducing vaccine against lutenizing hormone-releasing hormone (LHRH) caused drastic atrophy of the prostate in rodents Oayashankar et al, 1989;Rovan et al, 1992) and monkeys (Giri et al, 1991). The effectiveness of this vaccination is likely due to the downregulation of gonadotropins and testosterone and consequendy the atrophy of testosteronedependent organs such as the testes and prostate.…”

Section: Antibody-inducing Vaccinesmentioning

confidence: 99%

Effects of Androgen Ablation on Anti-Tumor Immunity

Kast¹

2004

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Public reporting burden for this collection of infometion is estimated to average 1 hour per response, including the tine for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of infbtmation. Androgen ablation (AA) constitutes the most common therapy for the treatment of advanced prostate Ceuicer.' While initially effective at reducing tumor burden, most patients recur with androgen insensitive disease. There exists a clear need to augment the clinical efficacy of hormone-based therapies, and imraunotherapy of prostate cancer represents a promising approach for achieving such augmentation. Moreover, our data indicate that AA affects the immune system both systemically as well as at the prostate. Castration of mice stimulates B and T lymphopoiesis, thymic and bone marrow hyperplasia. The induction of apoptotic cell death following androgen ablation is accompanied by an inflammatory infiltrate comprised predominantly of activated T cells. This AA induced autoimmune-like response exerts limited anti-tumor activity in a mouse prostate cancel model, but the anti-tumor effect is potentially synergistic with CTIiA-4 blockade, which promotes the development of autoreactive T cells. We have used the first year of this proposal to obtain and produce all necessary reagents (genes, tumor cell lines, hybridomas, purified antibodies) to position ourselves for studying the effects of AA on prostate cancer immunity as these effecs might significsmtly influence the ability of a tumor-bearing host to moxint an effective immune response. SUBJECT TERMS Page 4 IntroductionNormal and cancerous prostate cells require male sex hormones (androgens) for growth. Consequently, a common treatment for prostate cancer is androgen ablation (AA) therapy. Although AA constitutes an effective means for significantly reducing tumor burden and inducing a phase of remission of tumor growth in prostate cancer, a majority of treated patients recur with untreatable, androgen insensitive tumors. Consequently, there is a need for the development of new therapies that target prostate cancer cells via mechanisms that do not rely on the hormonal sensitivity of the cells. Yet the effectiveness of AA in reducing initial tumor burden makes its continued use likely, so new therapeutic approaches that provide synergistic anti-tumor effects when combined with AA would be attractive.Considerable interest has been directed recently toward the development of immimotherapeutic approaches for the treatment of malignancy, including prostate cancer. However, it is well established that sex hormones are potent regulators of the immune response and lymphocyte development. Since immune-based therapies will likely be administered in patients imdergoing AA therapy, the loss of androgen effects may influence the nature of the host immune response. In general, androgens suppress the immune response and, conversely, castration of mice increases their ability to reject transplanted t...

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Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat

Cited by 26 publications

References 14 publications

Highly Immunogenic and Totally Synthetic Lipopeptides as Self-Adjuvanting Immunocontraceptive Vaccines

Highly Immunogenic and Totally Synthetic Lipopeptides as Self-Adjuvanting Immunocontraceptive Vaccines

Induction of early and bioeffective antibody response in rodents with the luteinizing hormone-releasing hormone vaccine given as a single dose in biodegradable microspheres along with alum

Effects of Androgen Ablation on Anti-Tumor Immunity

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