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Bergman PJ. Cancer Immunotherapy. Vet Clin North Am Small Anim Pract 2024; 54:441-468. [PMID: 38158304 DOI: 10.1016/j.cvsm.2023.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
The enhanced understanding of immunology experienced over the last 5 decades afforded through the tools of molecular biology has recently translated into cancer immunotherapy becoming one of the most exciting and rapidly expanding fields. Human cancer immunotherapy is now recognized as one of the pillars of treatment alongside surgery, radiation, and chemotherapy. The field of veterinary cancer immunotherapy has also rapidly advanced in the last decade with a handful of commercially available products and a plethora of investigational cancer immunotherapies, which will hopefully expand our veterinary oncology treatment toolkit over time.
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Affiliation(s)
- Philip J Bergman
- Clinical Studies, VCA; Katonah Bedford Veterinary Center, Bedford Hills, NY, USA; Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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Abstract
The enhanced understanding of immunology experienced over the last 4 decades afforded through the tools of molecular biology has recently translated into cancer immunotherapy becoming one of the most exciting and rapidly expanding fields. Human cancer immunotherapy is now recognized as one of the pillars of treatment alongside surgery, radiation, and chemotherapy. The field of veterinary cancer immunotherapy has also rapidly advanced in the last decade with a handful of commercially available products and a plethora of investigational cancer immunotherapies that will hopefully expand the veterinary oncology treatment toolkit over time.
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Garg H, Hada RS, Gupta JC, Talwar GP, Dubey S. Combination immunotherapy with Survivin and luteinizing hormone-releasing hormone fusion protein in murine breast cancer model. World J Clin Oncol 2018; 9:188-199. [PMID: 30622927 PMCID: PMC6314864 DOI: 10.5306/wjco.v9.i8.188] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 08/24/2018] [Accepted: 11/04/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6leu)-LTB] for immunotherapy of breast cancer.
METHODS Murine 4T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.
RESULTS Preventive immunization with 20 µg recombinant Survivin and MIP was effective in suppressing growth of 4T-1 mouse model of breast cancer (P = 0.04) but 50 µg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.
CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.
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Affiliation(s)
- Himani Garg
- Talwar Research Foundation, Neb Sarai, New Delhi 110068, India
- Amity Institute of Virology and Immunology, Amity University Uttar Pradesh, Noida 201303, Uttar Pradesh, India
| | | | - Jagdish C Gupta
- Talwar Research Foundation, Neb Sarai, New Delhi 110068, India
| | - G P Talwar
- Talwar Research Foundation, Neb Sarai, New Delhi 110068, India
| | - Shweta Dubey
- Amity Institute of Virology and Immunology, Amity University Uttar Pradesh, Noida 201303, Uttar Pradesh, India
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Rima UK, Bari ASM, Hossain MZ, Khan MAH. Plasmid DNA vaccine coding eight repeats of gonadotrophin-releasing hormone induced atrophy of prostate in male mice. Prostate Int 2018; 6:151-156. [PMID: 30505818 PMCID: PMC6251954 DOI: 10.1016/j.prnil.2018.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 11/17/2017] [Accepted: 01/04/2018] [Indexed: 11/26/2022] Open
Abstract
Background Prostate hyperplasia and neoplasia are major illness of men and elderly dogs. Treatment of prostate cancer requires androgen deprivation surgery or therapy to prevent metastases and alleviate pain. Recently, six DNA vaccines have entered clinical trials against prostate cancer in humans with limited success. There is a need for new therapies that delay the establishment of malignancy and prolong survival. Materials and methods A plasmid DNA vaccine coding for eight gonadotrophin-releasing hormone (GnRH-I) interspersed in eight T-helper epitopes was used. Sexually mature male mice were immunized with the vaccine in hemagglutinating virus of Japanese envelope vector and boosted in nonionized surfactant vesicles in study weeks 0, 3, 6, 9, and 12. Plasma anti-GnRH-I antibody response, serum testosterone concentration, and effect on prostate were evaluated. Results Results of an indirect enzyme linked immunosorbent assay (ELISA) showed anti-GnRH-I antibody response (OD value) detected in the study week 3 (0.613 ± 0.179) with a highest response in the week 12 (1.205 ± 0.219). Serum testosterone concentration (ng/ml) in vaccinated mice was significantly reduced (P > 0.000, 0.761 ± 0.531) in the study week 24 in contrast to control serum (7.583 ± 1.251). Group average gross combined weight of prostate and seminal vesicles of vaccinated mice was significantly (P < 0.000) reduced in the study week 24 (319.75 ± 89.19 mg) in contrast to control weight (563.25 ± 108.60 mg). Sections of prostate stained with Goldner's trichrome showed profuse pink color secretion in control tubules, which however was absent in the vaccinated prostate. The lining epithelium of the vaccinated prostate was atrophied and did not enfold in its lumen. Conclusions Immunization strategy designed with the plasmid DNA vaccine in hemagglutinating virus of Japanese envelope and nonionized surfactant vesicles can be the genetic immunization platform. This vaccine bears potentials in terms of reducing serum testosterone concentration and induction of atrophy of prostate. Targeted ablation of native GnRH-I by genetic immunization could offer leverage to vaccinologists, seeking therapeutic target to control and prevent malignancy of prostate.
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Affiliation(s)
- Umme K Rima
- Department of Medicine, Surgery and Obstetrics, Faculty of Veterinary & Animal Science, Hajee Mohammad Danesh Science & Technology University, Dinajpur, Bangladesh
| | - Abu S M Bari
- Department of Pathology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Mohammad Z Hossain
- Department of Livestock Services, Ministry of Livestock and Fisheries, Bangladesh
| | - Mohammad A H Khan
- Department of Pathology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh
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Targeting luteinizing hormone-releasing hormone: A potential therapeutics to treat gynecological and other cancers. J Control Release 2018; 269:277-301. [DOI: 10.1016/j.jconrel.2016.11.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 11/04/2016] [Accepted: 11/05/2016] [Indexed: 01/05/2023]
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Effect of gonadotropin-releasing hormone vaccination on T lymphocyte changes in male rats. J Reprod Immunol 2017; 120:1-7. [PMID: 28196761 DOI: 10.1016/j.jri.2017.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 12/09/2016] [Accepted: 02/06/2017] [Indexed: 11/20/2022]
Abstract
The aim of this study was to detect the effect of immunization against gonadotropin-releasing hormone (GnRH) on cell-meditated immunity. Three-week-old male Sprague-Dawley rats (n=32) were randomly and equally assigned to two groups: 1) GnRH-tandem-ovalbumin immunized group; and 2) the control group (injected with an equivalent Al(OH)3 adjuvant). Blood samples were collected at two-week intervals to assess the level of GnRH-specific antibodies and testosterone. Moreover, blood and thymus samples were also collected to analyze the T lymphocyte subpopulations one and two months after the last booster immunization. T lymphocyte immunity against GnRH was activated during the first month post-immunization as exhibited by increased numbers of CD3+ (P<0.05) and CD4+ (P<0.05)T lymphocytes following testosterone suppression (P<0.01), which was then restored and maintained at appropriate levels in the second month. In contrast, the differentiation of T lymphocytes in the thymus was reduced during the first month after immunization as exhibited by the significant decreased number of CD3+ (P<0.05) cells, followed by the restoration and heightened numbers at later time points for both the number of CD3+ (P<0.05) and CD4+ (P<0.01)T lymphocytes. These results suggest that immunization against GnRH interferes with the number of lymphocytes during the early time points following immunization. The number of T lymphocytes initially decreased in the peripheral blood following immunization, but was replenished by newly exported cells from the thymus which eventually restored the T lymphocytes to normal levels.
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Naz RK, Saver AE. Immunocontraception for Animals: Current Status and Future Perspective. Am J Reprod Immunol 2015; 75:426-39. [PMID: 26412331 DOI: 10.1111/aji.12431] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 09/01/2015] [Indexed: 01/09/2023] Open
Abstract
An alternative to surgical sterilization for fertility control of animals (wild, zoo, farm, and domestic) is needed to prevent problems related to overpopulation, including culling and relocation. A PubMed and Google Scholar database search was conducted using the keywords 'contraceptive vaccine animals,' 'immunocontraception animals,' 'non-surgical sterilization animals,' 'PZP vaccine,' and 'GnRH vaccine.' The searches from 1972 to 2015 yielded over 1500 publications. These articles were read, and 375 were selected for detailed analysis. Articles referenced in these publications were also thoroughly examined. PZP and GnRH contraceptive vaccines (CVs) have been extensively investigated for fertility control of wild, zoo, farm, and domestic animal populations. Both vaccines have shown tremendous success with PZP vaccines taking the lead. Novel technologies and targets are being developed to improve existing vaccines and generate second-generation CVs. Single-shot vaccines, which can be delivered remotely, will greatly advance the field of immunocontraception for animal use with potential human application.
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Affiliation(s)
- Rajesh K Naz
- Reproductive Immunology and Molecular Biology Laboratory, Department of Obstetrics and Gynecology, School of Medicine, West Virginia University, Morgantown, WV, USA
| | - Ashley E Saver
- Reproductive Immunology and Molecular Biology Laboratory, Department of Obstetrics and Gynecology, School of Medicine, West Virginia University, Morgantown, WV, USA
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Su S, Sun X, Zhou X, Fang F, Li Y. Effects of GnRH immunization on the reproductive axis and thymulin. J Endocrinol 2015; 226:93-102. [PMID: 26016747 DOI: 10.1530/joe-14-0720] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/27/2015] [Indexed: 11/08/2022]
Abstract
The bidirectional regulation of thymulin in the reproductive-endocrine function of the hypothalamic-pituitary-gonadal (HPG) axis of rats immunized against GnRH remains largely unclear. We explored the alterations in hormones in the HPG axis in immunized rats to dissect the repressive effect of immunization on thymulin, and to clarify the interrelation of reproductive hormones and thymulin in vivo. The results showed that, in the first 2 weeks of booster immunization, thymulin was repressed when reproductive hormones were severely reduced. The self-feedback regulation of thymulin was then stimulated in later immune stages: the rising circulating thymulin upregulated LH and FSH, including GnRH in the hypothalamus, although the levels of those hormones were still significantly lower than in the control groups. In astrocytes, thymulin produced a feedback effect in regulated GnRH neurons. However, in the arcuate nucleus (Arc) and the median eminence (ME), the mediator of astrocytes and other glial cells were also directly affected by reproductive hormones. Thus, in immunized rats, the expression of glial fibrillary acidic protein was distinctly stimulated in the Arc and ME. This study demonstrated that thymulin was downregulated by immunization against GnRH in early stage. Subsequently, the self-feedback regulation was provoked by low circulating thymulin. Thereafter, rising thymulin levels promoted pituitary gonadotropins levels, while acting directly on GnRH neurons, which was mediated by astrocytes in a region-dependent manner in the hypothalamus.
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Affiliation(s)
- Shiping Su
- College of Animal Sciences and TechnologyAnhui Agricultural University, 130, Changjiang West Road, Hefei, Anhui 230036, People's Republic of ChinaCollege of Life ScienceFujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of ChinaThe Biotechnology Center of Anhui Agriculture UniversityHefei, People's Republic of China
| | - Xiaoxia Sun
- College of Animal Sciences and TechnologyAnhui Agricultural University, 130, Changjiang West Road, Hefei, Anhui 230036, People's Republic of ChinaCollege of Life ScienceFujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of ChinaThe Biotechnology Center of Anhui Agriculture UniversityHefei, People's Republic of China
| | - Xiuhong Zhou
- College of Animal Sciences and TechnologyAnhui Agricultural University, 130, Changjiang West Road, Hefei, Anhui 230036, People's Republic of ChinaCollege of Life ScienceFujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of ChinaThe Biotechnology Center of Anhui Agriculture UniversityHefei, People's Republic of China
| | - Fuigui Fang
- College of Animal Sciences and TechnologyAnhui Agricultural University, 130, Changjiang West Road, Hefei, Anhui 230036, People's Republic of ChinaCollege of Life ScienceFujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of ChinaThe Biotechnology Center of Anhui Agriculture UniversityHefei, People's Republic of China
| | - Yunsheng Li
- College of Animal Sciences and TechnologyAnhui Agricultural University, 130, Changjiang West Road, Hefei, Anhui 230036, People's Republic of ChinaCollege of Life ScienceFujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of ChinaThe Biotechnology Center of Anhui Agriculture UniversityHefei, People's Republic of China
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Chang C, Varamini P, Giddam AK, Mansfeld FM, D'Occhio MJ, Toth I. Investigation of Structure-Activity Relationships of Synthetic Anti-Gonadotropin Releasing Hormone Vaccine Candidates. ChemMedChem 2015; 10:901-10. [DOI: 10.1002/cmdc.201500036] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Indexed: 11/05/2022]
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Abstract
Tumor immunology and immunotherapy is one of the most exciting and rapidly expanding fields. The immune system is divided into 2 primary components: the innate immune response and the highly specific, but more slowly developing, adaptive or acquired immune response. Immune responses are separated by whether they are induced by exposure to a foreign antigen (active response) or transferred through serum or lymphocytes from an immunized individual (passive response). The ideal cancer immunotherapy agent should discriminate between cancer and normal cells (specificity), be potent enough to kill small or large numbers of tumor cells (sensitivity), and prevent recurrence of a tumor (durability).
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Affiliation(s)
- Philip J Bergman
- Clinical Studies, VCA, 546 Bedford Road, Bedford Hills, New York, NY 10507, USA; Department of Molecular Pharmacology & Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
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Detection of antibodies against customized epitope: use of a coating antigen employing VEGF as fusion partner. Appl Microbiol Biotechnol 2014; 98:6659-66. [PMID: 24595426 DOI: 10.1007/s00253-014-5618-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2013] [Revised: 02/10/2014] [Accepted: 02/11/2014] [Indexed: 10/25/2022]
Abstract
Diagnosis of many infectious, autoimmune diseases and cancers depends on the detection of specific antibodies against peptide epitope by enzyme-linked immunosorbent assay (ELISA). However, small peptides are difficult to be coated on the plate surfaces. In this study, we selected GnRH as a model hapten to evaluate whether VEGF121 would be suitable as an irrelevant hapten-carrier to develop a universal platform for specific antibodies detection. Firstly, GnRH was fused to the C terminus of VEGF121 and the resultant fusion protein VEGF-GnRH expressed effectively as inclusion bodies in Escherichia coli. Thereafter, VEGF-GnRH was easily purified to near homogeneity with a yield of about 235 mg from 2.1 L induced culture. At last, VEGF-GnRH was used to perform ELISA and western blot, and our results suggested that VEGF-GnRH was capable of detecting anti-GnRH antibodies in sera both qualitatively and quantitatively. Indeed, previous studies of our laboratory had demonstrated that other fusion proteins such as VEGF-Aβ10, VEGF-GRP, VEGF-CETPC, and VEGF-βhCGCTP37 were able to detect their corresponding antibodies specifically. Therefore, VEGF121 may be a suitable irrelevant fusion partner of important diagnostic peptide markers. Our works would shed some light on the development of a universal platform for detection of specific antibodies.
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EFFECTS OF A GONADOTROPIN-RELEASING HORMONE VACCINE ON OVARIAN CYCLICITY AND UTERINE MORPHOLOGY OF AN ASIAN ELEPHANT (ELEPHAS MAXIMUS). J Zoo Wildl Med 2012; 43:603-14. [DOI: 10.1638/2011-0270.1] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Virus-Like Particles as vaccine antigens and adjuvants: application to chronic disease, cancer immunotherapy and infectious disease preventive strategies. ACTA ACUST UNITED AC 2010. [DOI: 10.1016/j.provac.2010.07.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Abstract
The immune system is generally divided into 2 primary components: the innate immune response, and the highly specific but more slowly developing adaptive or acquired immune response. Immune responses can be further separated by whether they are induced by exposure to a foreign antigen (an "active" response) or whether they are transferred through serum or lymphocytes from an immunized individual (a "passive" response). The ideal cancer immunotherapy agent should be able to discriminate between cancer and normal cells (ie, specificity), be potent enough to kill small or large numbers of tumor cells (ie, sensitivity), and lastly be able to prevent recurrence of the tumor (ie, durability). Tumor immunology and immunotherapy is one of the most exciting and rapidly expanding fields at present.
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