Helix pomatia hemocyanin — A novel bio-adjuvant for viral and bacterial antigens

Gesheva, Vera; Chausheva, Stela; Stefanova, Nadia; Mihaylova, Nikolina; Doumanova, Lyuba; Idakieva, Krassimira; Tchorbanov, Andrey

doi:10.1016/j.intimp.2015.03.011

Cited by 18 publications

(17 citation statements)

References 27 publications

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“…Recently, molluscan hemocyanin has found applications as an antibacterial and antiviral factor owing to its potential phenoloxidase activity. These effects have been demonstrated in a number of reports [30,31,51,75,101]. H. pomatia hemocyanin was successfully used as a novel bioadjuvant for viral and bacterial antigens [101].…”

Section: Hemocyanin: the Main Protein Of Molluscan Hemolymphmentioning

confidence: 95%

“…These effects have been demonstrated in a number of reports [30,31,51,75,101]. H. pomatia hemocyanin was successfully used as a novel bioadjuvant for viral and bacterial antigens [101]. Furthermore, the effect of Hcs on various cancer cell lines has been studied, because their primary amino acid sequences are very different from mammalian ones.…”

Section: Hemocyanin: the Main Protein Of Molluscan Hemolymphmentioning

confidence: 99%

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Hemolymph of molluscan origin: from biochemistry to modern biomaterials science

Machałowski

Jesionowski

2020

Appl. Phys. A

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Molluscan hemolymph is a unique kind of body fluid, which in many respects is analogous to human blood, although there are several crucial differences. Here, for the first time, we critically analyze the prospects for applications of this fluid in modern biomaterials science. Particular attention is paid to the biochemistry and chemistry of molluscan hemolymph, as well as to hemocytes and hemocyanins as key functional players within this unique biological fluid. We focus on hemocytes as multifunctional hemolytic cells involved in immune response, and especially in the biomineralization process. The next part of the review contains a discussion of molluscan shell formation and regeneration from different points of view. Finally, we consider the challenges, solutions, and future directions in the application of molluscan hemolymph for bioinspired material chemistry and biomedicine.

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Section: Hemocyanin: the Main Protein Of Molluscan Hemolymphmentioning

confidence: 95%

Section: Hemocyanin: the Main Protein Of Molluscan Hemolymphmentioning

confidence: 99%

Hemolymph of molluscan origin: from biochemistry to modern biomaterials science

Machałowski

Jesionowski

2020

Appl. Phys. A

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“…Bioassay-guided investigations and in vivo models have demonstrated the antimicrobial (e.g., [45,73,74]), anticancer [48,75,76], anti-inflammatory [49,77,78], antispasmodic [79,80], neuromuscular blocking [81], wound-healing [82], and immunogenic [83,84] properties of molluscan extracts and purified compounds. At least 19 compounds of molluscan origin are currently part of the global marine pharmaceutical clinical pipeline and four are now FDA approved [51,85], including the powerful analgesic Ziconotide derived from the venom of Conus magus [86], a carnivorous cone snail, and three dolastatin derivatives originally sourced from the tissue of the sea hare Dolabella auricularia: Brentuximab vedotin [87] and Polatuzumab vedotin [88] for the treatment of hematologic cancers (e.g., Hodgkins lymphoma) and Enfortumab vedotin for urotherial cancer [89].…”

Section: Molluscs: a Wealth Of Potential Therapeutic Compoundsmentioning

confidence: 99%

“…Because of these versatile properties along with their large size (3.3-13.5 MDa), Hcs are regularly used as vaccine adjuvants and hapten carriers (subunit conjugates) [103]. As biomolecules, they are also considered safer than synthetic adjuvants (e.g., aluminium derivatives) [83]. Keyhole limpet hemocyanin (KLH) from the marine gastropod Megathura crenulata (Fissurellidae) is the most extensively used Hc, and is commercially available to biomedical researchers for vaccine development and immunological studies [103] (Tables S3 and S4).…”

Section: Molluscan Hemocyanins As Therapeutic Adjuvants and Model Antmentioning

confidence: 99%

Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease

et al. 2020

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Respiratory diseases place an immense burden on global health and there is a compelling need for the discovery of new compounds for therapeutic development. Here, we identify research priorities by critically reviewing pre-clinical and clinical studies using extracts and compounds derived from molluscs, as well as traditional molluscan medicines, used in the treatment of respiratory diseases. We reviewed 97 biomedical articles demonstrating the anti-inflammatory, antimicrobial, anticancer, and immunomodulatory properties of >320 molluscan extracts/compounds with direct relevance to respiratory disease, in addition to others with promising bioactivities yet to be tested in the respiratory context. Of pertinent interest are compounds demonstrating biofilm inhibition/disruption and antiviral activity, as well as synergism with approved antimicrobial and chemotherapeutic agents. At least 100 traditional medicines, incorporating over 300 different mollusc species, have been used to treat respiratory-related illness in cultures worldwide for thousands of years. These medicines provide useful clues for the discovery of bioactive components that likely underpin their continued use. There is particular incentive for investigations into anti-inflammatory compounds, given the extensive application of molluscan traditional medicines for symptoms of inflammation, and shells, which are the principal molluscan product used in these preparations. Overall, there is a need to target research toward specific respiratory disease-related hypotheses, purify bioactive compounds and elucidate their chemical structures, and develop an evidence base for the integration of quality-controlled traditional medicines.

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“…However, its production relies fully on a single natural source because the recombinant production of hemocyanin has been unsuccessful to date; this limited availability has prompted significant interest in studying other hemocyanins. Thus, gastropod hemocyanins from Concholepas concholepas (CCH) [12], Fissurella latimarginata (FLH) [13], Haliotis tuberculata [14], Helix pomatia [15], and Rapana venosa [16, 17], which have been extensively characterized in terms of their biochemical properties and immunomodulatory/adjuvant effects, have emerged as potential candidates to complement or substitute for KLH [1, 18].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapeutic Potential of Mollusk Hemocyanins in Combination with Human Vaccine Adjuvants in Murine Models of Oral Cancer

Román

Campo

Villar

et al. 2019

Journal of Immunology Research

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Mollusk hemocyanins have been used for decades in immunological and clinical applications as natural, nontoxic, nonpathogenic, and nonspecific immunostimulants for the treatment of superficial bladder cancer, as carriers/adjuvants of tumor-associated antigens in cancer vaccine development and as adjuvants to dendritic cell-based immunotherapy, because these glycoproteins induce a bias towards Th1 immunity. Here, we analyzed the preclinical therapeutic potential of the traditional keyhole limpet hemocyanin (KLH) and two new hemocyanins from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH) in mouse models of oral squamous cell carcinoma. Due to the aggressiveness and deadly malignant potential of this cancer, the hemocyanins were applied in combination with adjuvants, such as alum, AddaVax, and QS-21, which have been shown to be safe and effective in human vaccines, to potentiate their antitumor activity. The immunogenic performance of the hemocyanins in combination with the adjuvants was compared, and the best formulation was evaluated for its antitumor effects in two murine models of oral cancer: MOC7 cells implanted in the flank (heterotopic) and bioluminescent AT-84 E7 Luc cells implanted in the floor of the mouth (orthotopic). The results demonstrated that the hemocyanins in combination with QS-21 showed the greatest immunogenicity, as reflected by a robust, specific humoral response predominantly characterized by IgG2a antibodies and a sustained cellular response manifesting as a delayed hypersensitivity reaction. The KLH- and FLH-QS-21 formulations showed reduced tumor development and greater overall survival. Hemocyanins, as opposed to QS-21, had no cytotoxic effect on either oral cancer cell line cultured in vitro, supporting the idea that the antitumor effects of hemocyanins are associated with their modulation of the immune response. Therefore, hemocyanin utilization would allow a lower QS-21 dosage to achieve therapeutic results. Overall, our study opens a new door to further investigation of the use of hemocyanins plus adjuvants for the development of immunotherapies against oral carcinoma.

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Helix pomatia hemocyanin — A novel bio-adjuvant for viral and bacterial antigens

Cited by 18 publications

References 27 publications

Hemolymph of molluscan origin: from biochemistry to modern biomaterials science

Hemolymph of molluscan origin: from biochemistry to modern biomaterials science

Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease

Immunotherapeutic Potential of Mollusk Hemocyanins in Combination with Human Vaccine Adjuvants in Murine Models of Oral Cancer

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