HOCl Oxidation-modified CT26 Cell Vaccine Inhibits Colon Tumor Growth in a Mouse Model

Huang, Wenjun; Ma, Cong; Zhou, Yan; Yao, Yuqin; Wang, Yuxi; Gou, Lantu; Chen, Yi; Yang, Jin

doi:10.7314/apjcp.2012.13.8.4037

Cited by 11 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypochlorous acid (HOCl) as an endogenous strong oxidant plays a significant role in human immunity, − which is generated from the reaction of H 2 O 2 with Cl – catalyzed by heme enzyme myeloperoxidase released by activated phagocytes in defense against invading pathogens. , However, the excessive or unintended production of HOCl in vivo has been implicated in numerous diseases including atherosclerosis, arthritis, and some cancers associated with inflammation. − It is known that HOCl can attack proteins, lipids, and DNA, and the obtained products are generally irreversible, thus leading to the damage of the normal cell and tissue. − …”

Section: Introductionmentioning

confidence: 99%

Reaction Mechanisms of Histidine and Carnosine with Hypochlorous Acid Along with Chlorination Reactivity of N-Chlorinated Intermediates: A Computational Study

Han

Zhou

Liu

et al. 2022

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Hypochlorous acid (HOCl) released from activated leukocytes not only plays a significant role in the human immune system but is also implicated in numerous diseases including atherosclerosis and some cancers due to its inappropriate production. Histidine (His) and carnosine (Car), as a respective mediator and protective agent of HOCl damage, have attracted considerable attention; however, their detailed reaction mechanisms are still unclear. In this study, using a His residue with two peptide bond groups (HisRes) as a model, the reaction mechanisms of HisRes and Car including NεH and NδH tautomers with HOCl along with the chlorination reactivity of N-chlorinated intermediates were investigated by quantum chemical methods. The obtained results indicate that in the imidazole side chain, the pyridine-like N is the most reactive site rather than the pyrrole-like N, and the kinetic order of all of the possible reaction sites in HisRes follows pyridine-like N > imidazole Cδ ≫ imidazole Cε > pyrrole-like N, while that in Car is pyridine-like N ≫ imidazole Cδ ≫ amide N. As for N-chlorinated intermediates at imidazole, although the unprotonated form has a low chlorination reactivity as expected, it can still chlorinate tyrosine. Especially, the protonated form exhibits similar ability to HOCl, causing secondary damage in vivo. N-Chlorinated Car features higher internal chlorine migration ability than its intermolecular transchlorination, preventing further HOCl-induced damage. Additionally, a generally overlooked nucleophilic Cl– shift is also found in N-chlorinated Car/HisRes, indicating that nucleophilic sites in biomolecules also need to be considered. The outcomes of this study are expected to expand our understanding of secondary damage and protective mechanisms involved in HOCl in humans.

show abstract

Section: Introductionmentioning

confidence: 99%

Reaction Mechanisms of Histidine and Carnosine with Hypochlorous Acid Along with Chlorination Reactivity of N-Chlorinated Intermediates: A Computational Study

Han

Zhou

Liu

et al. 2022

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…HOCl is an oxidant that has been demonstrated to participate in immunogenic modulation, and it can increase the immunogenicity of antigens through oxidation modifications, that increase recognition, capture and processing by APCs [ [34] , [35] , [36] , [37] , [38] , [39] , [40] ]. Chiang et al showed that compared to the traditional methods, such as freeze-thaw cycles and UVB-irradiation to treat tumor cells, HOCl-oxidation induces rapid primary necrotic tumor cell death, protein oxidation, and increased expression of chaperones and antioxidant proteins, leading to activation of oxidative stress-response pathways [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

Zhou

et al. 2022

Bioactive Materials

View full text Add to dashboard Cite

Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16–F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.

show abstract

“…The present study identified HOCl as the most promising candidate in terms of toxicity and induction of immunogenic danger molecules (such as CRT) in cancer cells. HOCl was previously shown to enhance the immunogenicity of colorectal cancer cells in vivo, prevent distant metastasis of human melanoma cells, and alter antigen-presenting machinery and the cross-priming of tumor material (66)(67)(68)(69)(70). This makes HOCl a promising candidate as an adjuvant in peritoneal cancer therapy outside the current vaccination strategies against ovarian cancer employed with this type of ROS (71).…”

Section: Discussionmentioning

confidence: 99%

Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells

Freund

Miebach

Stope³

et al. 2021

Oncol Rep

View full text Add to dashboard Cite

Tumors of the abdominal cavity, such as colorectal, pancreatic and ovarian cancer, frequently metastasize into the peritoneum. Large numbers of metastatic nodules hinder curative surgical resection, necessitating lavage with hyperthermic intraperitoneal chemotherapy (HIPEC). However, HIPEC not only causes severe side effects but also has limited therapeutic efficacy in various instances. At the same time, the age of immunotherapies such as biological agents, checkpoint-inhibitors or immune-cell therapies, increasingly emphasizes the critical role of anticancer immunity in targeting malignancies. The present study investigated the ability of three types of long-lived reactive species (oxidants) to inactivate cancer cells and potentially complement current HIPEC regimens, as well as to increase tumor cell expression of danger signals that stimulate innate immunity. The human abdominal cancer cell lines HT-29, Panc-01 and SK-OV-3 were exposed to different concentrations of hydrogen peroxide (H 2 O 2), hypochlorous acid (HOCl) and peroxynitrite (ONOO-). Metabolic activity was measured, as well as determination of cell death and danger signal expression levels via flow cytometry and detection of intracellular oxidation via high-content microscopy. Oxidation of tumor decreased intracellular levels of the antioxidant glutathione and induced oxidation in mitochondria, accompanied by a decrease in metabolic activity and an increase in regulated cell death. At similar concentrations, HOCl showed the most potent effects. Non-malignant HaCaT keratinocytes were less affected, suggesting the approach to be selective to some extent. Pro-immunogenic danger molecules were investigated by assessing the expression levels of calreticulin (CRT), and heat-shock protein (HSP)70 and HSP90. CRT expression was greatest following HOCl and ONOOtreatment, whereas HOCl and H 2 O 2 resulted in the greatest increase in HSP70 and HSP90 expression levels. These results suggested that HOCl may be a promising agent to complement current HIPEC regimens targeting peritoneal carcinomatosis.

show abstract

HOCl Oxidation-modified CT26 Cell Vaccine Inhibits Colon Tumor Growth in a Mouse Model

Cited by 11 publications

References 26 publications

Reaction Mechanisms of Histidine and Carnosine with Hypochlorous Acid Along with Chlorination Reactivity of N-Chlorinated Intermediates: A Computational Study

Reaction Mechanisms of Histidine and Carnosine with Hypochlorous Acid Along with Chlorination Reactivity of N-Chlorinated Intermediates: A Computational Study

Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

Hypochlorous acid selectively promotes toxicity and the expression of danger signals in human abdominal cancer cells

Contact Info

Product

Resources

About