Intensive therapy with gastropodan hemocyanins increases their antitumor properties in murine model of colon carcinoma

Stoyanova, Emiliya; Mihaylova, Nikolina; Manoylov, Iliyan; Bradyanova, Silviya; Raynova, Yuliana; Idakieva, Krassimira; Tchorbanov, Andrey

doi:10.1016/j.intimp.2020.106566

Cited by 7 publications

(12 citation statements)

References 32 publications

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“…The same approach of treatment with Hcs (KLH, CCH, or FLH) in a B16F10 mouse model of melanoma resulted in variety of immune responses among the Hcs, probably directed to the different carbohydrate content [15]. We also observed the dominance of immune responses depending on RtH or HpH administration within the same therapeutic schedule in the C-26 murine model of colorectal carcinoma [21].…”

Section: Introductionsupporting

confidence: 54%

“…Using three different schemes of administration (mild, intensive, and upon priming), both Hcs exhibited a strong anti-cancer effect with changing efficiency relative to the schemes. Immunization of experimental animals with RtH or HpH generated high levels of tumor-specific antibodies and Cytotoxic T lymphocytes (CTL), as well as the secretion of proinflammatory cytokines, leading to inhibition of tumor development and increased survival [20,21]. The same approach of treatment with Hcs (KLH, CCH, or FLH) in a B16F10 mouse model of melanoma resulted in variety of immune responses among the Hcs, probably directed to the different carbohydrate content [15].…”

Section: Introductionmentioning

confidence: 99%

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Antitumor Properties of Epitope-Specific Engineered Vaccine in Murine Model of Melanoma

et al. 2022

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Finding new effective compounds of natural origin for composing anti-tumor vaccines is one of the main goals of antitumor research. Promising anti-cancer agents are the gastropodan hemocyanins–multimeric copper-containing glycoproteins used so far for therapy of different tumors. The properties of hemocyanins isolated from the marine snail Rapana thomasiana (RtH) and the terrestrial snail Helix aspersa (HaH) upon their use as carrier-proteins in conjugated vaccines, containing ganglioside mimotope GD3P4 peptide, were studied in the developed murine melanoma model. Murine melanoma cell line B16F10 was used for solid tumor establishment in C57BL/6 mice using various schemes of therapy. Protein engineering, flow cytometry, and cytotoxicity assays were also performed. The administration of the protein-engineered vaccines RtH-GD3P4 or HaH-GD3P4 under the three different regimens of therapy in the B16F10 murine melanoma model suppressed tumor growth, decreased tumor incidence, and prolonged the survival of treated animals. The immunization of experimental mice induced an infiltration of immunocompetent cells into the tumors and generated cytotoxic tumor-specific T cells in the spleen. The treatment also generates significantly higher levels of tumor-infiltrated M1 macrophages, compared to untreated tumor-bearing control mice. This study demonstrated a promising approach for cancer therapy having potential applications for cancer vaccine research.

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Section: Introductionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Antitumor Properties of Epitope-Specific Engineered Vaccine in Murine Model of Melanoma

et al. 2022

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“…Hemocyanin from the gastropod Megathura crenulata , known as keyhole limpet hemocyanin (KLH), has been widely used in these biomedical applications [6, 7]. However, the limited availability of KLH has led to the exploration of new gastropod hemocyanins, such as the hemocyanins from Concholepas concholepas (CCH) [8] and Fissurella latimarginata (FLH) [9], among others [10, 11]. We previously demonstrated that CCH had antitumor properties similar to those of KLH in a bladder cancer model [12].…”

Section: Introductionmentioning

confidence: 99%

C‐type lectin receptors MR and DC‐SIGN are involved in recognition of hemocyanins, shaping their immunostimulatory effects on human dendritic cells

et al. 2021

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Hemocyanins are used as immunomodulators in clinical applications because they induce a strong Th1‐biased cell‐mediated immunity, which has beneficial effects. They are multiligand glycosylated molecules with abundant and complex mannose‐rich structures. It remains unclear whether these structures influence hemocyanin‐induced immunostimulatory processes in human APCs. We have previously shown that hemocyanin glycans from Concholepas concholepas (CCH), Fissurella latimarginata (FLH), and Megathura crenulata (KLH), participate in their immune recognition and immunogenicity in mice, interacting with murine C‐type lectin receptors (CLRs). Here, we studied the interactions of these hemocyanins with two major mannose‐binding CLRs on monocyte‐derived human DCs: MR (mannose receptor) and DC‐SIGN (DC‐specific ICAM‐3–grabbing nonintegrin). Diverse analyses showed that hemocyanins are internalized by a mannose‐sensitive mechanism. This process was calcium dependent. Moreover, hemocyanins colocalized with MR and DC‐SIGN, and were partly internalized through clathrin‐mediated endocytosis. The hemocyanin‐mediated proinflammatory cytokine response was impaired when using deglycosylated FLH and KLH compared to CCH. We further showed that hemocyanins bind to human MR and DC‐SIGN in a carbohydrate‐dependent manner with affinity constants in the physiological concentration range. Overall, we showed that these three clinically valuable hemocyanins interact with human mannose‐sensitive CLRs, initiating an immune response and promoting a Th1 cell‐driving potential.

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“…Further research revealed that HMC may be a novel and important non-specific innate immune defense molecule (2,3). It has been reported that HMC could be functionally converted into phenoloxidase (4) antimicrobial peptides (5)(6)(7)(8), antiviral (9)(10)(11)(12), antitumor agent (13)(14)(15)(16)(17), antifungal (18), agglutinin (19,20), hemolysin (21), and regulatory proteins (22,23). Moreover, our previous findings indicated that HMC from shrimp Litopenaeus vannamei reacted with human Ig as an antigen (5,19,24) and acted as an immune-enhancing protein (25,26).…”

Section: Introductionmentioning

confidence: 99%

Protein Diversity and Immune Specificity of Hemocyanin From Shrimp Litopenaeus vannamei

et al. 2021

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Hemocyanin is an important non-specific innate immune defense molecule with phenoloxidase, antiviral, antibacterial, hemolytic, and antitumor activities. To better understand the mechanism of functional diversity, proteomics approach was applied to characterize hemocyanin (HMC) expression profiles from Litopenaeus vannamei. At first, hemocyanin was purified by Sephadex G-100 and DEAE-cellulose (DE-52) columns from shrimp serum, and 34 protein spots were identified as HMC on the 2-DE gels. Furthermore, we found that 9 HMC spots about 75 or 77 kDa were regulated by Streptococcus agalactiae and Vibrio parahaemolyticus infection at 6, 12, and 24 h. In addition, 6 different pathogen-binding HMC fractions, viz., HMC-Mix, HMC-Vp, HMC-Va, HMC-Vf, HMC-Ec, and HMC-Sa, showed different agglutinative and antibacterial activities. Moreover, lectin-blotting analysis showed significant differences in glycosylation level among HMC isomers and bacteria-binding HMC fractions. Particularly, the agglutinative activities of the HMC fractions were almost completely abolished when HMC was deglycosylated by O-glycosidase, which suggest that O-linked sugar chains of HMC played important roles in the innate immune recognition. Our findings demonstrated for the first time that L. vannamei HMC had molecular diversity in protein level, which is closely associated with its ability to recognize diverse pathogens, whereas glycan modification probably contributed to HMC’s diversity and multiple immune activities.

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Intensive therapy with gastropodan hemocyanins increases their antitumor properties in murine model of colon carcinoma

Cited by 7 publications

References 32 publications

Antitumor Properties of Epitope-Specific Engineered Vaccine in Murine Model of Melanoma

Antitumor Properties of Epitope-Specific Engineered Vaccine in Murine Model of Melanoma

C‐type lectin receptors MR and DC‐SIGN are involved in recognition of hemocyanins, shaping their immunostimulatory effects on human dendritic cells

Protein Diversity and Immune Specificity of Hemocyanin From Shrimp Litopenaeus vannamei

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