scholarly journals pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity

2019 ◽  
Author(s):  
Janessa Wehr ◽  
Eden L. Sikorski ◽  
Elizabeth Bloch ◽  
Mary S. Feigman ◽  
Noel J. Ferraro ◽  
...  
Keyword(s):  
Immune System ◽  
Human Serum ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Wide Range ◽  
Ph Dependent

A growing class of immunotherapeutic agents work by redirecting components of the immune system to recognize specific markers on the surface of cancer cells and initiate a selective immune response. However, such immunotherapeutic modalities will remain confined to a relatively small subgroup of patients until two major hurdles are overcome: (1) the specific targeting of cancer cells relative to healthy cells, and (2) the lack of common targetable tumor biomarkers among all patients. Here, we designed a unique class of agents that exploit the inherent acidic microenvironment of solid tumors to selectively graft the surface of cancer cells with immuno-engager epitopes for directed destruction by components of the immune system. Specifically, conjugates were assembled using an antigen that recruit antibodies present in human serum, and the pH(Low) Insertion Peptide (pHLIP), a unique peptide that selectively target tumors in vivo by anchoring onto cancer cell surfaces in a pH-dependent manner. We established that conjugates can recruit antibodies from human serum to the surface of cancer cells, and induce complement-dependent and antibody-dependent cellular cytotoxicity by peripheral blood mononuclear cells and also an engineered NK cell line. These results suggest that these agents have the potential to be applicable to treating a wide range of solid tumors and to circumvent the problem of narrow windows of selectivity.

scholarly journals Characterization of a Rhodanese Homologue from Haemonchus Contortus and its Immune-Modulatory Effects on Goat Immune Cells in Vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Parasitic Nematodes ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Suppression and modulation of the immune response of the host by nematode parasites have been reported widely. Rhodaneses or thiosulfate: cyanide sulfurtransferases are present in a wide range of organisms, such as archea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homology could bind by goat peripheral blood mononuclear cells (PBMCs) in vivo.Results: In the present study, we cloned and produced recombinant rhodanese protein originated from Haemonchus contortus (rHCRD), which was one of the parasitic nematodes of small ruminants. The effect of this protein on modulating the immunity of goat PBMC and monocyte was studied in the current work. The predominant localization of the natural HCRD protein was verified as the bowel wall and body surface of worms, according to the immunohistochemical tests. It was proved in this study that the serum produced by artificially infecting goats with H. contortus successfully recognized rHCRD which conjugated goat PBMCs. The rHCRD was co-incubated with goat PBMCs to observe the immunomodulatory effect on proliferation, apoptosis and secretion of cytokines exerted by HCRD. The results showed that the interaction of rHCRD suppressed proliferation of goat PBMCs stimulated by ConA but did not induce the apoptosis of goat PBMCs. After rHCRD exposure, the production of TNF-α and IFN-γ were significantly decreased, however, it significantly increased the secretion of IL-10 and TGF-β1 in goat PBMCs. Phagocytotic assay by FITC-dextran internalization showed that rHCRD inhibited the phagocytosis of goat monocytes. Moreover, rHCRD could down-regulate the expression of MHC-II on goat monocytes in a dose-dependent manner. Conclusions: These discoveries proposed a possible target as immunomodulator, which was potentially beneficial to illuminate the interaction between parasites and hosts in the molecular level and hunt for innovative protein species as candidate targets of drug and vaccine.

scholarly journals Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Mhc I ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD downregulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression.Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

scholarly journals Effects of FR-91 on Immune Cells from Healthy Individuals and from Patients with Non-Hodgkin Lymphoma

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
V. R. M. Lombardi ◽  
E. Martínez ◽  
R. Chacón ◽  
I. Etcheverría ◽  
R. Cacabelos
Keyword(s):  
Immune System ◽  
Hodgkin Lymphoma ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Lymphocyte Activation ◽  
Dependent Manner ◽  
Healthy Individuals ◽  
Peripheral Blood Mononuclear ◽  
Non Hodgkin Lymphoma

The immune system is subject to destruction and dysfunction as a result of attacks by pathogenic and environmental agents. In addition, many clinical situations exist in which it is desirable to stimulate or suppress the immune system. The present study evaluated the screening efficacy of flow cytometric lymphocyte subset typing in peripheral blood mononuclear cells from healthy individuals (HI) and from patients with non-Hodgkin lymphoma (NHL) treated with different concentrations of FR-91, a standardized lysate of microbial cells belonging to the Bacillus genus, andin vitrocytokine production. Increased expression of subset markers (CD3, CD4, CD8) in NHL and CD3 in HI suggests an immunomodulating effect of FR-91. In addition the results of cytokine production also demonstrated a clear effect of FR-91 on both populations. A significant increase of IL-6, IL-12, IFN-γand TNF-αwas observed in the HI group after treatment with FR-91. In a similar manner an increase of IL-2, IL-6, IL-12, IFN-γand TNF-αwas also observed in the NHL group. In conclusion FR-91 seems to affect lymphocyte subpopulations,in vitrocytokine production, as well as mitogen-induced lymphocyte activation in a dose-dependent manner in both healthy individuals and NHL patients.

scholarly journals Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Mhc I ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD down-regulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression. Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

scholarly journals Effect of Vasoactive Intestinal Peptide (VIP) on NKG2D Signal Pathway and Its Contribution to Immune Escape of MKN45 Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chong Wang ◽  
Xi-Jin Zhou ◽  
Yuan-yuan Li ◽  
Juan Wan ◽  
Le-ying Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Nk Cells ◽  
Cancer Cells ◽  
Mononuclear Cells ◽  
Immune Escape ◽  
Nk Cell ◽  
Signal Molecules ◽  
Gastric Cancer Cells ◽  
Peripheral Blood Mononuclear

Objective. To investigate VIP effect on the cytotoxicity of NK cell to gastric cancer cellsin vitroand the relation between the effect with the NKG2D signal molecules in NK cells.Material and Methods. NK cells were purified from peripheral blood mononuclear cells (PBMC). Before and after NK cells were incubated with VIP or its antagonist (D-p-Cl-Phe6,Leu17)-VIP, we detected the cytotoxicity of NK cells to MKN45 gastric cancer cells by MTT and detected the expressions of NKG2D, DAP10, and NF-κB proteins and mRNAs in NK cells by immunocytochemistry and RT-PCR in those conditions. Then we analyzed the effect of VIP and its antagonist on the cytotocicity of NK cell to gastric cancer cells and on expressions of NKG2D, DAP10, and NF-κB signal molecules in NK cells.Results. VIP could inhibit the cytotoxicity of NK cells to MKN45 cells and could inhibit the expressions of NKG2D, DAP10, and NF-κB in NK cells. However, (D-p-Cl-Phe6, Leu17)-VIP could reverse those effects.Conclusions. The VIP inhibited the cytotoxicity of NK cell to MKN45 cells which might get through inhibiting the expressions of NKG2D signal molecules in NK cells. This may be one mechanism of gastric cancer cells escaping organism immune clearance.

scholarly journals Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

2020 ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Mhc I ◽  
Nematode Parasites ◽  
Candidate Drug ◽  
Wide Range

Abstract Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD down-regulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression.Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

scholarly journals Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yujian Wang ◽  
Muhammad Ehsan ◽  
Jianmei Huang ◽  
Kalibixiati Aimulajiang ◽  
RuoFeng Yan ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Mononuclear Cells ◽  
Small Ruminants ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Mhc I ◽  
Nematode Parasites ◽  
Wide Range

Abstract Background Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo. Methods In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion. Results We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD downregulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression. Conclusions These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

scholarly journals Chitosan-Coated Gold Nanoparticles Induce Low Cytotoxicity and Low ROS Production in Primary Leucocytes, Independent of Their Proliferative Status

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 942
Author(s):  
Helen Yarimet Lorenzo-Anota ◽  
Diana G. Zarate-Triviño ◽  
Jorge Alberto Uribe-Echeverría ◽  
Andrea Ávila-Ávila ◽  
José Raúl Rangel-López ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Lymphoid Cells ◽  
Ros Production ◽  
Biomedical Sciences ◽  
Peripheral Blood Mononuclear

(1) Background: Chitosan-coated gold nanoparticles (CH-AuNPs) have important theranostic applications in biomedical sciences, including cancer research. However, although cell cytotoxicity has been studied in cancerous cells, little is known about their effect in proliferating primary leukocytes. Here, we assessed the effect of CH-AuNPs and the implication of ROS on non-cancerous endothelial and fibroblast cell lines and in proliferative lymphoid cells. (2) Methods: The Turkevich method was used to synthetize gold nanoparticles. We tested cell viability, cell death, ROS production, and cell cycle in primary lymphoid cells, compared with non-cancer and cancer cell lines. Concanavalin A (ConA) or lipopolysaccharide (LPS) were used to induce proliferation on lymphoid cells. (3) Results: CH-AuNPs presented high cytotoxicity and ROS production against cancer cells compared to non-cancer cells; they also induced a different pattern of ROS production in peripheral blood mononuclear cells (PBMCs). No significant cell-death difference was found in PBMCs, splenic mononuclear cells, and bone marrow cells (BMC) with or without a proliferative stimuli. (4) Conclusions: Taken together, our results highlight the selectivity of CH-AuNPs to cancer cells, discarding a consistent cytotoxicity upon proliferative cells including endothelial, fibroblast, and lymphoid cells, and suggest their application in cancer treatment without affecting immune cells.

scholarly journals Stimulation of production of prostaglandin E in gingival cells exposed to products of human blood mononuclear cells

1981 ◽  
Vol 198 (2) ◽  
pp. 391-396 ◽  
Author(s):  
S M D'Souza ◽  
D J Englis ◽  
A Clark ◽  
R G Russell
Keyword(s):  
Mononuclear Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Gingival Tissue ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Gingival Cells ◽  
Stimulation Of

1. Supernatant media from cultures of unstimulated human peripheral blood mononuclear cells contained one or more factors that increased by several hundred-fold the production of prostaglandin E by fibroblast-like cells derived from both inflamed and normal human gingival tissue. 2. This stimulation occurred in a dose-dependent manner and was completely inhibited by 14 microM-indomethacin. 3. Responsiveness to the factor declined as the age of the cell culture increased. 4. An increase in prostaglandin E production was first observed after a 2h exposure to the mononuclear cell factor(s) and could be prevented by cycloheximide. 5. Brief exposure (0.5 and 1.0 h) to mononuclear cell factor did not increase prostaglandin E production by the cells in a subsequent 72 h incubation in the absence of mononuclear cell factor. 6. Addition of arachidonate (10 microM and 15 microM) further enhanced stimulation of prostaglandin E production in response to mononuclear cell factor. 7. The stimulatory activity was resistant to digestion by trypsin, but was heat-labile, so that only 17% remained after treatment at 56 degrees C for 30 min.

scholarly journals Metabolomic profiles of plasma and uterine luminal fluids from healthy and repeat breeder Holstein cows

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Natsumi Funeshima ◽  
Ryotaro Miura ◽  
Taiga Katoh ◽  
Hikari Yaginuma ◽  
Takeshi Kitou ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Plasma Metabolites ◽  
Dependent Manner ◽  
Interferon Tau ◽  
Peripheral Blood Mononuclear ◽  
Metabolomic Profiling ◽  
Reproductive Disorder ◽  
Uterine Fluid ◽  
Reduced Rate ◽  
Repeat Breeder

Abstract Background Repeat breeding is a critical reproductive disorder in cattle. The problem of repeat breeder cattle remains largely unmanageable due to a lack of informative biomarkers. Here, we utilized metabolomic profiling in an attempt to identify metabolites in the blood plasma and uterine luminal fluids. We collected blood and uterine fluid from repeat breeder and healthy cows on day 7 of the estrous cycle. Results Metabolomic analysis identified 17 plasma metabolites detected at concentrations that distinguished between the two groups, including decreased various bile acids among the repeat breeders. However, no metabolites that varied significantly were detected in the uterine luminal fluids between two groups. Among the plasma samples, kynurenine was identified as undergoing the most significant variation. Kynurenine is a metabolite produced from tryptophan via the actions of indoleamine 2,3-dioxygenase (IDO). As IDO is key for maternal immune tolerance and induced in response to interferon tau (IFNT, ruminant maternal recognition of pregnancy factor), we examined the responsiveness to IFNT on peripheral blood mononuclear cells (PBMC) isolated from healthy and repeat breeder cows. The mRNA expression of IFNT-response makers (ISG15 and MX2) were significantly increased by IFNT treatment in a dose-dependent manner in both groups. Although treatment with IFNT promoted the expression of IDO in PBMCs from both groups, it did so at a substantially reduced rate among the repeat breeder cows, suggesting that decreased levels of kynurenine may relate to the reduced IDO expression in repeat breeder cows. Conclusions These findings provide valuable information towards the identification of critical biomarkers for repeat breeding syndrome in cattle.

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