Dihydroartemisinin shift the immune response towards Th1, inhibit the tumor growth in vitro and in vivo

2011 ◽  
Vol 271 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Shokoofe Noori ◽  
Zuhair M. Hassan
Keyword(s):  
Immune Response ◽  
Tumor Growth

Programming the anti-tumor immune response in vitro and its application to stop the growth of tumor cells and prolonging the lifespan of mice with carcinoma in vivo

2017 ◽  
pp. 67-73
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
О.П. Буданова ◽  
И.Ю. Малышев
Keyword(s):  
Immune Response ◽  
Tumor Growth ◽  
Tumor Cells ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Ec Cells ◽  
Growth Of Tumor ◽  
Immune Response In Vitro

Цель - представить доказательства правомерности гипотезы, что комбинированный пул репрограммированных in vitro макрофагов и лимфоцитов будет эффективно ограничивать пролиферацию опухолевых клеток in vitro , а при введении в организм будет существенно ограничивать развитие опухоли in vivo . Методика. Размножение опухолевых клеток инициировали in vitro путем добавления клеток карциномы Эрлиха (КЭ) в среду культивирования RPMI-1640. Развитие асцитной опухоли in vivo воспроизводили путем внутрибрюшной инъекции клеток КЭ мышам. Результаты. Установлено, что M3 макрофаги вместе с антиген-репрограммированными лимфоцитами оказывают выраженный противоопухолевый эффект и in vitro, и in vivo , который был существеннее противоопухолевого эффекта цисплатина. Заключение. Факты, свидетельствующие, что М3 макрофаги в сочетании с in vitro антиген-репрограммированными лимфоцитами значительно подавляют рост опухоли in vivo , делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли путем предварительного программирования противоопухолевого иммунного ответа «в пробирке». Aim. To test a hypothesis that a combined pool of in vitro reprogrammed macrophages and lymphocytes will effectively limit growth of tumor cells in vitro , and injections of these cells into the body will considerably limit development of a tumor in vivo . Methods. Tumor growth was initiated in vitro by addition of Ehrlich carcinoma (EC) cells to the RPMI-1640 cell culture medium and in vivo by intraperitoneal injection of EC cells into mice. Results. M3 macrophages in combination with antigen-reprogrammed lymphocytes exerted a pronounced antitumor effect both in vitro and in vivo, which was superior to the effect of cisplatin. Conclusion. M3 macrophages in combination with in vitro antigen-reprogrammed lymphocytes significantly inhibited the tumor growth in vivo . This fact justifies development of a clinical version of the tumor growth restricting biotechnology using pre-programming of the antitumor immune response in vitro .

scholarly journals TMOD-32. GL261 LUCIFERASE-EXPRESSING CELLS ELICIT AN ANTI-TUMOR IMMUNE RESPONSE: AN EVALUATION OF MURINE GLIOMA MODELS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi269-vi270
Author(s):  
Victoria Sanchez ◽  
John Lynes ◽  
Stuart Walbridge ◽  
Xiang Wang ◽  
Nancy Edwards ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Tumor Growth ◽  
Median Survival ◽  
In Vivo Evaluation ◽  
Kaplan Meier ◽  
Long Term Survivors

Abstract Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. Intracranially injected GL261 cells are widely used as an immunocompetent animal model of glioma, but it is common practice to transfect these with luciferase to facilitate tumor monitoring during treatment. Our group has previously shown that the luciferase-expressing GL261 Red-FLuc cells create an inflammatory response when implanted intracranially. Now, we additionally explore the inflammatory response of GL261-Luc2 cells and demonstrate a similar host immune response occurs with this model as well. In our in vivo evaluation, C57BL/6 mice underwent stereotaxic, intracranial implantation with GL261, GL261 Red-FLuc or GL261-Luc2 cells at doses of 5x104cells/5mL or 3x105cells/5uL.MRIs were performed to monitor relative tumor growth. To assess intrinsic differences between cell lines, in vitro cytokine profiles were evaluated by proteome microarray. Kaplan-Meier survival analyses demonstrated median survival for mice implanted with GL261 cells at 5x104cells was 18 to 21 days. The GL261-Red FLuc implanted mice cells did not reach median survival at either tumor dose with greater than 60% of mice termed long-term survivors. Finally, mice injected with GL261-Luc2 cells at 3x105cells reached median survival at 23 days, but median survival was significantly prolonged for mice implanted with GL261-Luc2 at a dose of 5x104cells (37 days, with 40% becoming long-term survivors) compared to GL261 implanted mice. MRIs reveal differences in tumor growth that correspond with the differences in median survival between groups. In addition, proteomic analyses revealed significantly elevated inflammatory cytokines such as IFN-gamma, IL-7 and TNF-alpha in the supernatants of the GL261 Red-FLuc cells and GL261-Luc2 cells. Further immune characterization is ongoing. Our data suggests that GL261 Red-FLuc and GL261-Luc2 murine models elicit an anti-tumor immune response by increasing pro-inflammatory modulators which stimulate the tumoricidal function of immune cells in the tumor microenvironment.

scholarly journals 869 Locally administered immunotherapy self-delivering RNAi PH-762 results in abscopal clearance of untreated distal tumors, suggesting systemic immune response, in a murine hepatocarcinoma model

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A910-A910
Author(s):  
Benjamin Cuiffo ◽  
Melissa Maxwell ◽  
Dingxue Yan ◽  
Brianna Rivest ◽  
James Cardia ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Growth ◽  
Mechanism Of Action ◽  
Systemic Toxicity ◽  
Published Data ◽  
Abscopal Effect ◽  
Systemic Immune Response ◽  
In Vivo Efficacy

BackgroundThe development of locally administered immune checkpoint inhibition (ICI) holds potential promise for enhanced activity and decreased systemic toxicity, but such an approach is challenging with the available ICI antibodies. We have previously shown that the intratumoral (IT) delivery of PH-762, a self-delivering RNAi compound targeting PD-1 based on proprietary INTASYL™ technology, can significantly inhibit tumor growth associated with changes in the immune cell population in the tumor microenvironment towards an anti-tumor phenotype. We present data showing that IT administration of PH-762 not only inhibits local tumor growth but can also elicit an abscopal effect in distal untreated tumors. The in vivo efficacy and in vitro mechanism of action support the generation of a PH-762 driven systemic anti-tumor immune response. Therefore, ICI using INTASYL is an alternative to antibody drugs for immunotherapy.MethodsTo assess in vivo efficacy, Hepa1–6 cells were implanted subcutaneously into the flanks of C57BL/6J mice. Vehicle (PBS) or murine targeting PH-762 (mPH-762) were administered IT on Days 1, 4, 7, 10 and 14. To determine an abscopal effect cells were also implanted into the opposite flank but left untreated. Tumor volumes and body weights were recorded. In addition, in vitro mechanism of action studies were performed with CD3-stimulated human pan T cells. PD-1 mRNA knockdown was assessed by qRT-PCR; PD-1 protein expression by flow cytometry; and T cell function by cytokine release.ResultsTreatment with IT administered mPH-762 significantly inhibited tumor growth compared with vehicle treated control tumors. Furthermore, the growth of the untreated bilateral tumor was significantly reduced with 80% of these tumors showing complete regression. Mechanism of action studies showed potent and durable silencing of PD-1. Increased release of IFN-γ, CXCL10, and IL-6 and suppression of IL-10 release were indicators of an enhanced immune response.ConclusionsThese data show that silencing PD-1 with IT administration of mPH-762 not only inhibits growth of treated tumors but elicits an abscopal effect leading to cure of distal tumors. This data and other recently published data showing evidence of a specific antitumor immune response in a tumor rechallenge model after prior treatment with INTASYL compounds, demonstrate the desired systemic immune response can be obtained with local administration of PH-762. INTASYL represent an alternative to antibody therapy for IT checkpoint blockade with potential for improved efficacy and reduced systemic toxicity which will be investigated in an upcoming clinical trial.

SS6-7 The C-terminal decapeptide of prothymosin α induces a TH1-type immune response in vitro and retards tumor growth in vivo

Cytokine ◽  
2010 ◽  
Vol 52 (1-2) ◽  
pp. 47
Author(s):  
Kyriaki Ioannou ◽  
Pinelopi Samara ◽  
Nadia Kavrochorianou ◽  
Christina Bega ◽  
George Thyphronitis ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Growth ◽  
Prothymosin Α ◽  
Immune Response In Vitro

C5a Complement Depletion Suppresses In Vivo B Lymphoma Progression and Enhances Development Of Cellular Anti-Tumor Immune Response

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1837-1837
Author(s):  
Suresh Veeramani ◽  
George J. Weiner
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cd8 T Cells ◽  
B Lymphoma

Abstract Background Proteins within the complement system have complex effects on cellular immune responses. In previous studies, we found that active complement components, especially C5a, can dampen the development of antigen-specific immune responses following vaccination with a model antigen, in part by promoting generation of APC-induced T regulatory (Treg) cells. These studies also demonstrated that B lymphoma cell lines exposed to complement can induce Treg generation in vitro. The current study was designed to address whether depletion of C5a could enhance development of a cellular anti-lymphoma immune response in vivo. Methods Immunocompetent Balb/C mice were inoculated subcutaneously with syngeneic A20 B lymphoma cells mixed with either 10 μg of rat anti-mouse C5a monoclonal antibody (mAb) or 10 μg of isotype-matched Rat IgG2a control mAb. Tumor growth was followed. In select experiments, mice were sacrificed and analyzed for the percentage and activity of tumor-infiltrating T cells and A20-specific splenic T cell responses. Results 1. Tumor progression. Lymphoma grew more slowly in mice treated with anti-C5a mAb compared to mice treated with control mAb (p<0.05) {Fig. 1). 2. Intratumoral T cells. Tumors from mice treated with anti-C5a mAb had higher CD8+ T cell infiltration compared to mice treated with control mAb (p=0.002) (Fig. 2). Tumor-infiltrating CD8+ T cells showed a trend towards higher intracellular IFNg production in mice treated with anti-C5a mAb compared to control mAb (p=0.051). 3. Splenic T cells. Splenic T cells from mice treated with anti-C5a mAb produced IFNg to a greater degree than did splenic T cells from control mice when splenocytes were cultured with irradiated A20 cells in vitro (p=0.041) (Fig. 3). There was a trend towards decreased numbers of splenic CD4+CD25highFoxp3+ Tregs in C5a-depleted mice compared to control mice. Conclusions Depletion of C5a at the site of tumor inoculation slows tumor growth and increases the number of tumor infiltrating CD8 T cells in a syngenic immunocompetent model of lymphoma. A trend towards enhanced production of IFNg in the tumor infiltrating T cells, increased numbers of tumor-specific splenic T cells, and reduced numbers of splenic Tregs, suggests intratumoral C5a depletion can enhance tumor-specific immune responses both within the tumor and systemically. Ongoing studies are exploring the molecular mechanisms involved in C5a-promoted tumor progression and the use of C5a depletion as a novel strategy to improve anti-tumor immunity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fusion Protein Vaccine Based on Ag85B and STEAP1 Induces a Protective Immune Response against Prostate Cancer

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 786
Author(s):  
Linpei Guo ◽  
Hui Xie ◽  
Zheng Zhang ◽  
Zhun Wang ◽  
Shuanghe Peng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Tumor Microenvironment ◽  
Fusion Protein ◽  
Tumor Growth ◽  
Western Blotting ◽  
Protein Vaccine ◽  
Cancer Management

(1) Background: There are currently limited treatments for castration-resistant prostate cancer. Immunotherapy involving Sipuleucel-T has increasingly drawn attention for prostate cancer management. BCG plays a vital role in treating bladder cancer, mainly by inducing immune activation, but is rarely used for prostate cancer. (2) Methods: The TCGA database, PCR, and Western blotting were used to analyze the expression of STEAP1 in mouse and human tissues. Then, we constructed a fusion protein vaccine with Mycobacterium tuberculosis Ag85B and three repeated octapeptide epitopes of a six-transmembrane epithelial antigen of the prostate 1 (STEAP1186-193), Ag85B-3×STEAP1186-193. The uptake of the fusion protein vaccine by DCs was evaluated by confocal microscopy, and DC markers were detected using flow cytometry after incubation with the fusion protein. The immune response against prostate cancer was evaluated by the LDH assay and xenografts in vitro and in vivo. Then, the tumor microenvironment was determined using IHC and ELISA. In addition, the epitope was mutated using CRISPR-Cas9 to illustrate that the fusion protein elicited immunization against STEAP1. (3) Results: The TCGA database analysis, PCR, and Western blotting showed that STEAP1 was highly expressed in human and murine prostate cancer. After the uptake of the purified fusion protein vaccine by DCs, CD11c, CD80, CD86, and MHC II were upregulated and triggered a cytotoxic T lymphocyte (CTL) response against TRAMP-C1 and RM1 cells in vitro. Furthermore, the fusion protein vaccine inhibited tumor growth and improved the tumor microenvironment in vivo, with more CD3+ cells and fewer FOXP3+ cells in the tumor. Serum IFN-γ and IL-2 were significantly higher than in the control group, while IL-4 expression was lower, indicating that the fusion protein vaccine activated Th1 immunity. The immune response against prostate cancer was greatly suppressed when the antigen targets were knocked out using CRISPR-Cas9. (4) Conclusion: In summary, our results provide the first evidence that a vaccine based on a fusion protein consisting of Ag85B and a prostate cancer octapeptide epitope with complete Freund’s adjuvant (CFA), triggers a robust immune response and inhibits tumor growth in murine prostate cancer.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

The Inhibition Effect of Caveolin-1 on PANC1 Human Pancreatic Tumor Growth In vitro and In vivo*

2012 ◽  
Vol 38 (12) ◽  
pp. 1121-1131
Author(s):  
Xiao-Hui WANG ◽  
Ya-Min ZHENG ◽  
Ye-Qing CUI ◽  
Shuang LIU ◽  
Hai-Chen SUN ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Pancreatic Tumor ◽  
Caveolin 1 ◽  
Inhibition Effect

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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