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Preliminary Evaluation of an Autologous Dendritic Cell Vaccine Using Nanoparticle Technology for the Treatment of Canine Malignant Melanoma

Received: 3 February 2021     Accepted: 10 February 2021     Published: 23 February 2021
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Abstract

Canine malignant melanoma is an aggressive neoplasm that carries a poor prognosis due to its minimal responsiveness to traditional therapy protocols, particularly if the oral cavity, mucocutaneous junctions, or subungual sites are involved. This proof-of-concept study evaluated a prototype autologous dendritic cell vaccine using poly-lactic-co-glycolic (PLGA) nanoparticles containing antigens from patient-derived whole tumor lysate and the adjuvant monophosphoryl lipid A in five canines with stages III-IV malignant melanoma. Nanoparticle constructs biochemical characterization; encapsulation efficiency and kinetic release studies were determined. Our results showed that tumor antigens were successfully incorporated in the PLGA/monophosphoryl lipid A nanoparticle constructs. Additional in vitro experiments showed that the PLGA/monophosphoryl lipid A nanoparticle constructs effectively activated autologous dendritic cells, and generated a greater than twofold increase in the release of the pro-immune cytokine IFN-γ. No significant adverse effects were observed in any of the patients following intradermal vaccination, and flow cytometry of whole blood revealed increased CD4:CD8 T lymphocyte ratios by the completion of the study. These results suggest that a dendritic cell vaccine utilizing PLGA/monophosphoryl lipid A nanoparticle technology could potentially initiate an adaptive immune response and is safe to administer to canine patients. Further in vivo studies with a larger cohort of patients are warranted.

Published in American Journal of Biomedical and Life Sciences (Volume 9, Issue 1)
DOI 10.11648/j.ajbls.20210901.21
Page(s) 84-96
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Melanoma, Nanoparticles, Dendritic Cells, Adaptive Immunity, Cancer Vaccines

References
[1] Atherton MJ, Morris JS, McDermott MR, and Lichty BD. Cancer immunology and canine malignant melanoma: A comparative review. Veterinary Immunol Immunopathol 2016, 169, 15-26.
[2] Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, Mendoza TR, Hay J, Atkinson TM, Abernethy AP, Bruner DW, Cleeland CS, Sloan JA, Chilukuri R, Baumgartner P, Denicoff A, St. Germain D, O'Mara AM, Chen A, Kelaghan J, Bennett AV, Sit L, Rogak L, Barz A, Paul DB and Schrag D. Development of the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). JNCI 2014, 106, 1-11.
[3] Bergman PJ, Camps-Palau MA, McKnight JA, Leibman NF, Craft DM, Leung C, Liao J, Riviere I, Sadelain M, Hohenhaus AE, Gregor P, Houghton AN, Perales MA, and Wolchok JD. Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 2006, 24, 4582-4585.
[4] Boston SE, Lu X, Culp WT, Montinaro V, Romanelli G, Dudley RM, Liptak JM, Mestrinho LA, Buracco P. Efficacy of systemic adjuvant therapies administered to dogs after excision of oral malignant melanomas: 151 cases (2001-2012). JAVMA 2014, 245, 401-407.
[5] Brockley LK, Cooper MA and Bennett PF. Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival. NZVJ 2013, 61, 25-31.
[6] Butterfield LH. Dendritic cells in cancer immunotherapy clinical trials: are we making progress? Front Immunol 2013, 4, 1-7.
[7] Chiang CL, Benencia F, and Coukos G. Whole Tumor Antigen Vaccines. Semin Immunol 2010, 22, 132-143.
[8] Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, and Preat V. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release 2012, 161, 505-522.
[9] Elamanchili P, Lutsiak CME, Hamdy S, Diwan M, and Samuel J. “Pathogen-Mimicking” Nanoparticles for Vaccine Delivery to Dendritic Cells. J Immunother 2007, 30, 378-395.
[10] Fan Y, and Moon JJ. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy. Vaccines 2015, 3, 662-685.
[11] Field G and Jackson TA. 2007. The Laboratory Canine, 1st ed. Taylor & Francis, Florida.
[12] Grosenbaugh DA, Leard AT, Bergman PJ, Klein MK, Meleo K, Susaneck S, Hess PR, Jankowski MK, Jones PD, Leibman NF, Johnson MH, Kurzman ID, and Wolchok JD. Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor. AJVR 2011, 72, 1631-1638.
[13] Guldner D, Hwang, JK, Cardieri MCD, Eren M, Ziaei P, Norton MG, and Souza CD. In Vitro Evaluation of the Biological Responses of Canine Macrophages Challenged with PLGA Naoparticles Containing Monophosphoryl Lipid A. PloS ONE 2016, 11, 1-20.
[14] Gutzwiller MER, Moulin HR, Zurbriggen A, Roosje P, and Summerfield A. Comparative analysis of canine monocyte- and bone-marrow-derived dendritic cells. Vet Res 2010, 41, 1-12.
[15] Hamdy S, Haddadi A, Shayeganpour A, Samuel J and Lavasanifar A. Activation of antigen-specific T cell-responses by mannan-decorated PLGA nanoparticles. Pharm Res 2011, 28, 2288-2301.
[16] Hernandez B, Adissu HA, Wei BR, Michael HT, Merlino G, and Simpson RM. Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas. Int J Mol Sci 2018, 19, 1-19.
[17] Hobart M, Ramassar V, Goes N, Urmson J, and Halloran PF. IFN regulatory factor-1 plays a central role in the regulation of the expression of class I and II MHC genes in vivo. J Immol 1997, 158, 4260-4269.
[18] Horiuchi Y, Tominaga M, Ichikawa M, Yamashita M, Okano K, Jikumaru Y, Nariai Y, Nakajima Y, Kuwabara M, and Yukawa M. Relationship between regulatory and type 1 T cells in dogs with oral malignant melanoma. Microbiol Immunol 2010, 54, 152-159.
[19] Klippstein R and Pozo D. Nanotechnology-based manipulation of dendritic cells for enhanced immunotherapy strategies. Nanomedicine 2010, 6, 523-529.
[20] MacEwen EG, Patnaik AK, Harbey HJ, Hayes AA and Matus R. Canine oral melanoma: comparison of surgery versus surgery plus Corynebacterium parvum. Cancer Invest 1986, 4, 397-402.
[21] MacEwen EG, Kurzman ID, Vail DM, Dubielziq RR, Everlith K, Mdewell BR, Rodriguez CO Jr, Phillips B, Zwahlen CH, Obradovich J, Rosenthal RC, Fox LE, Rosenberg M, Henry C, and Fidel J. Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl-tripeptide, and granulocyte macrophage colony-stimulating factor. Clin Cancer Res 1999, 5, 4249-4258.
[22] Maekawa N, Konnai S, Takagi S, Kagawa Y, Okagawa T, Nishimori A, Ikebuchi R, Izumi Y, Deguchi T, Nakajima C, Kato Y, Yamamoto K, Uemura H, Suzuki Y, Murata S, and Ohashi K. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma. Sci Rep 2017, 7, 1-12.
[23] Meyer A, Gruber AD and Klopfleisch R. CD25 Is expressed by canine cutaneous mast cell tumors but not by cutaneous connective tissue mast cells. Vet Pathol 2012, 49, 988-997.
[24] Nakai N, Hartmann G, Kishimoto S, and Katoh N. Dendritic cell vaccination in human melanoma: relationships between clinical effects and vaccine parameters. Pigment Cell Melanoma Res 2010, 23, 607-619.
[25] O’Connor CM and H. Wilson-Robles. Developing T Cell Cancer Immunotherapy in the Dog with Lymphoma. ILAR J 2014, 55, 169-181.
[26] O’Neill K, Guth A, Biller B, Elmslie R, and Dow S. Changes in regulatory T cells in dogs with cancer and association with tumor type. JVIM 2009, 23, 875-881.
[27] Ottnod JM, Smedley RC, Walshaw R, Hauptman JG, Kiupel M and Obradovich JE. A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma. Vet Comp Oncol 2013, 11, 219-229.
[28] Prasad S, Cody V, Saucier-Sawyre JK, Saltzman WM, Sasaki CT, Edelson RL, Birchall MA, and Hanlon DJ. Polymer nanoparticles containing tumor lysates as antigen delivery vehicles for dendritic cell-based anti-tumor immunotherapy. Nanomedicine 2011, 7, 1-10.
[29] Reis e Sousa C. Activation of dendritic cells: translating innate into adaptive immunity. Curr Opin Immunol 2004, 16, 21-25.
[30] Sahin U and Türeci Ӧ. Personalized vaccines for cancer immunotherapy. Science 2018, 359, 1355-1360.
[31] Salcedo M, Bercovici N, Taylor R, Vereecken P, Massicard S, Duriau D, Vernel-Pauillac F, Boyer A, Baron-Bodo V, Mallard E, Bartholeyns J, Goxe B, Latour N, Leroy S, Prigent D, Martiat P, Sales F, Laporte M, Bruyns C, Romet-Lemonne JL, Abastado JP, Lehmann F and Velu T. Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate. Cancer Immunol Immunother 2006, 55, 819-829.
[32] Sarti F, Perera G, Hintzen F, Kotti K, Krageorgiou V, Kammona O, Kiparissides C, and Bernkop-Schnurch A. In vivo evidence of oral vaccination with PLGA nanoparticles containing the immunostimulant monophosphoryl lipid A. Biomaterials 2011, 32, 4052-4057.
[33] Smedley RC, Lamoureux J, Sledge DG and Kiupel M. Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms. Veterinary Pathology 2011, 48, 32-40.
[34] Solbrig CM, Saucier-Sawyer JK, Cody V. Saltzman WM, and Hanlon DJ. Polymer nanoparticles for immunotherapy from encapsulated tumor-associated antigens and whole tumor cells. Mol Pharm 2007, 4, 47-57.
[35] Tamura K, Yamada M, Isotani M, Arai H, Yagihara H, Ono K, Washizu T, and Bonkobara M. Induction of dendritic cell-mediated immune responses against canine malignant melanoma cells. Vet J 2008, 175, 126-129.
[36] Treggiari E, Grant, JP and North SM. A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma. J Vet Med Sci 2016, 78, 845-850.
[37] Trepiakas R, Berntsen A, Hadrup SR, Bjorn J, Geertsen PF, Straten PT, Andersen MH, Pedersen AE, Soleimani A, Lorentzen T, Johansen JS, and Svane IM. Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial. Cytotherapy 2010, 12, 721-734.
[38] Uto T, Akagi T, Hamasaki T, Akashi M and Baba M. Modulation of innate and adaptive immunity by biodegradable nanoparticles. Immunol Lett 2009, 125, 46-52.
[39] Waeckerle-Men Y and Groettrup M. PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines. Adv Drug Deliv Rev 2005, 57, 475-482.
[40] Withrow SJ and Vail DM. 2007. Withrow & MacEwen’s Small Animal Clinical Oncology, 4th ed. Saunders, Missouri.
Cite This Article
  • APA Style

    Meaghan Veronica Eren, Julianne Hwang, Janean Fidel, Rance Sellon, Cleverson de Souza. (2021). Preliminary Evaluation of an Autologous Dendritic Cell Vaccine Using Nanoparticle Technology for the Treatment of Canine Malignant Melanoma. American Journal of Biomedical and Life Sciences, 9(1), 84-96. https://doi.org/10.11648/j.ajbls.20210901.21

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    ACS Style

    Meaghan Veronica Eren; Julianne Hwang; Janean Fidel; Rance Sellon; Cleverson de Souza. Preliminary Evaluation of an Autologous Dendritic Cell Vaccine Using Nanoparticle Technology for the Treatment of Canine Malignant Melanoma. Am. J. Biomed. Life Sci. 2021, 9(1), 84-96. doi: 10.11648/j.ajbls.20210901.21

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    AMA Style

    Meaghan Veronica Eren, Julianne Hwang, Janean Fidel, Rance Sellon, Cleverson de Souza. Preliminary Evaluation of an Autologous Dendritic Cell Vaccine Using Nanoparticle Technology for the Treatment of Canine Malignant Melanoma. Am J Biomed Life Sci. 2021;9(1):84-96. doi: 10.11648/j.ajbls.20210901.21

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  • @article{10.11648/j.ajbls.20210901.21,
      author = {Meaghan Veronica Eren and Julianne Hwang and Janean Fidel and Rance Sellon and Cleverson de Souza},
      title = {Preliminary Evaluation of an Autologous Dendritic Cell Vaccine Using Nanoparticle Technology for the Treatment of Canine Malignant Melanoma},
      journal = {American Journal of Biomedical and Life Sciences},
      volume = {9},
      number = {1},
      pages = {84-96},
      doi = {10.11648/j.ajbls.20210901.21},
      url = {https://doi.org/10.11648/j.ajbls.20210901.21},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbls.20210901.21},
      abstract = {Canine malignant melanoma is an aggressive neoplasm that carries a poor prognosis due to its minimal responsiveness to traditional therapy protocols, particularly if the oral cavity, mucocutaneous junctions, or subungual sites are involved. This proof-of-concept study evaluated a prototype autologous dendritic cell vaccine using poly-lactic-co-glycolic (PLGA) nanoparticles containing antigens from patient-derived whole tumor lysate and the adjuvant monophosphoryl lipid A in five canines with stages III-IV malignant melanoma. Nanoparticle constructs biochemical characterization; encapsulation efficiency and kinetic release studies were determined. Our results showed that tumor antigens were successfully incorporated in the PLGA/monophosphoryl lipid A nanoparticle constructs. Additional in vitro experiments showed that the PLGA/monophosphoryl lipid A nanoparticle constructs effectively activated autologous dendritic cells, and generated a greater than twofold increase in the release of the pro-immune cytokine IFN-γ. No significant adverse effects were observed in any of the patients following intradermal vaccination, and flow cytometry of whole blood revealed increased CD4:CD8 T lymphocyte ratios by the completion of the study. These results suggest that a dendritic cell vaccine utilizing PLGA/monophosphoryl lipid A nanoparticle technology could potentially initiate an adaptive immune response and is safe to administer to canine patients. Further in vivo studies with a larger cohort of patients are warranted.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - Preliminary Evaluation of an Autologous Dendritic Cell Vaccine Using Nanoparticle Technology for the Treatment of Canine Malignant Melanoma
    AU  - Meaghan Veronica Eren
    AU  - Julianne Hwang
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    T2  - American Journal of Biomedical and Life Sciences
    JF  - American Journal of Biomedical and Life Sciences
    JO  - American Journal of Biomedical and Life Sciences
    SP  - 84
    EP  - 96
    PB  - Science Publishing Group
    SN  - 2330-880X
    UR  - https://doi.org/10.11648/j.ajbls.20210901.21
    AB  - Canine malignant melanoma is an aggressive neoplasm that carries a poor prognosis due to its minimal responsiveness to traditional therapy protocols, particularly if the oral cavity, mucocutaneous junctions, or subungual sites are involved. This proof-of-concept study evaluated a prototype autologous dendritic cell vaccine using poly-lactic-co-glycolic (PLGA) nanoparticles containing antigens from patient-derived whole tumor lysate and the adjuvant monophosphoryl lipid A in five canines with stages III-IV malignant melanoma. Nanoparticle constructs biochemical characterization; encapsulation efficiency and kinetic release studies were determined. Our results showed that tumor antigens were successfully incorporated in the PLGA/monophosphoryl lipid A nanoparticle constructs. Additional in vitro experiments showed that the PLGA/monophosphoryl lipid A nanoparticle constructs effectively activated autologous dendritic cells, and generated a greater than twofold increase in the release of the pro-immune cytokine IFN-γ. No significant adverse effects were observed in any of the patients following intradermal vaccination, and flow cytometry of whole blood revealed increased CD4:CD8 T lymphocyte ratios by the completion of the study. These results suggest that a dendritic cell vaccine utilizing PLGA/monophosphoryl lipid A nanoparticle technology could potentially initiate an adaptive immune response and is safe to administer to canine patients. Further in vivo studies with a larger cohort of patients are warranted.
    VL  - 9
    IS  - 1
    ER  - 

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Author Information
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA

  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA

  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA

  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA

  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA

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