scholarly journals ON THE PROBLEM OF DEVELOPMENT OF THE UNIVERSAL IMMUNOTHERAPEUTIC ANTICANCER VACCINE

2018 ◽  
Vol 63 (3) ◽  
pp. 374-381
Author(s):  
A. I. Zinchenko ◽  
A. S. Schokolova ◽  
L. L. Birichevskaya
Keyword(s):  
Dendritic Cells ◽  
Treatment Method ◽  
Intratumoral Injection ◽  
Mutant Proteins ◽  
Cpg Dinucleotides ◽  
Tumor Bed ◽  
In Situ Activation ◽  
Cyclic Diguanosine Monophosphate ◽  
Diguanosine Monophosphate ◽  
Cellular Immune

The authors of this paper theoretically substantiated the cancer treatment method, using in situ activation of dendritic cells with intratumoral injection of two molecular “danger signals” of bacterial origin – plasmid DNA containing unmethylated CpG-dinucleotides and cyclic diguanosine monophosphate (cyclo-diGMP). Based on literature data it might be presumed that this procedure is capable to release from the dying cancer cells a large number of tumor-associated mutant proteins, to recruit effector immune cells into the tumor bed, to activate dendritic cells and as a result to induce a potent anti-cancer T-cellular immune response leading to elimination of both primary solid tumors and possible metastases. 

scholarly journals Combined Treatment of Murine Fibrosarcoma with Chemotherapy (Paclitaxel), Radiotherapy, and Intratumoral Injection of Dendritic Cells

2014 ◽  
Vol 26 (1) ◽  
pp. 53 ◽  
Author(s):  
Ji-Won Byun ◽  
Hyeon-Sook Lee ◽  
Sun-Uk Song ◽  
Si-Won Lee ◽  
Soon-Ki Kim ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Combined Treatment ◽  
Intratumoral Injection ◽  
Murine Fibrosarcoma

scholarly journals Degradation of cyclic diguanosine monophosphate by a hybrid two-component protein protects Azoarcus sp. strain CIB from toluene toxicity

2016 ◽  
Vol 113 (46) ◽  
pp. 13174-13179 ◽  
Author(s):  
Zaira Martín-Moldes ◽  
Blas Blázquez ◽  
Claudine Baraquet ◽  
Caroline S. Harwood ◽  
María T. Zamarro ◽  
...  
Keyword(s):  
Aromatic Hydrocarbons ◽  
Response Regulator ◽  
Anaerobic Growth ◽  
Two Component System ◽  
Component System ◽  
Bacterial Physiology ◽  
Toxic Concentration ◽  
Two Component ◽  
Cyclic Diguanosine Monophosphate ◽  
Diguanosine Monophosphate

Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger that controls diverse functions in bacteria, including transitions from planktonic to biofilm lifestyles, virulence, motility, and cell cycle. Here we describe TolR, a hybrid two-component system (HTCS), from the β-proteobacterium Azoarcus sp. strain CIB that degrades c-di-GMP in response to aromatic hydrocarbons, including toluene. This response protects cells from toluene toxicity during anaerobic growth. Whereas wild-type cells tolerated a sudden exposure to a toxic concentration of toluene, a tolR mutant strain or a strain overexpressing a diguanylate cyclase gene lost viability upon toluene shock. TolR comprises an N-terminal aromatic hydrocarbon-sensing Per–Arnt–Sim (PAS) domain, followed by an autokinase domain, a response regulator domain, and a C-terminal c-di-GMP phosphodiesterase (PDE) domain. Autophosphorylation of TolR in response to toluene exposure initiated an intramolecular phosphotransfer to the response regulator domain that resulted in c-di-GMP degradation. The TolR protein was engineered as a functional sensor histidine kinase (TolRSK) and an independent response regulator (TolRRR). This classic two-component system (CTCS) operated less efficiently than TolR, suggesting that TolR was evolved as a HTCS to optimize signal transduction. Our results suggest that TolR enables Azoarcus sp. CIB to adapt to toxic aromatic hydrocarbons under anaerobic conditions by modulating cellular levels of c-di-GMP. This is an additional role for c-di-GMP in bacterial physiology.

scholarly journals Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2878-2885 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Scott Barbuto ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
Amitabha Mazumder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Th17 Cells ◽  
T Helper ◽  
Tumor Bed ◽  
Distinct Lineage ◽  
Human Dendritic Cells ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.

scholarly journals Evaluation of Feline Monocyte-Derived Dendritic Cells Loaded with Internally Inactivated Virus as a Vaccine against Feline Immunodeficiency Virus

2008 ◽  
Vol 15 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Giulia Freer ◽  
Donatella Matteucci ◽  
Paola Mazzetti ◽  
Francesca Tarabella ◽  
Valentina Catalucci ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Functions ◽  
Peripheral Blood Mononuclear ◽  
Challenge Virus ◽  
Homologous Virus ◽  
Antibody Titers ◽  
Cellular Immune ◽  
Antigen Presenting

ABSTRACT Dendritic cells are the only antigen-presenting cells that can present exogenous antigens to both helper and cytolytic T cells and prime Th1-type or Th2-type cellular immune responses. Given their unique immune functions, dendritic cells are considered attractive “live adjuvants” for vaccination and immunotherapy against cancer and infectious diseases. The present study was carried out to assess whether the reinjection of autologous monocyte-derived dendritic cells loaded with an aldithriol-2-inactivated primary isolate of feline immune deficiency virus (FIV) was able to elicit protective immune responses against the homologous virus in naive cats. Vaccine efficacy was assessed by monitoring immune responses and, finally, by challenge with the homologous virus of vaccinated, mock-vaccinated, and healthy cats. The outcome of challenge was followed by measuring cellular and antibody responses and viral and proviral loads and quantitating FIV by isolation and a count of CD4+/CD8+ T cells in blood. Vaccinated animals exhibited clearly evident FIV-specific peripheral blood mononuclear cell proliferation and antibody titers in response to immunization; however, they became infected with the challenge virus at rates comparable to those of control animals.

scholarly journals Intratumoral injection of dendritic cells derived in vitro in patients with metastatic cancer

Cancer ◽  
2000 ◽  
Vol 89 (12) ◽  
pp. 2646-2654 ◽  
Author(s):  
Pierre L. Triozzi ◽  
Reema Khurram ◽  
Wayne A. Aldrich ◽  
Michael J. Walker ◽  
Julian A. Kim ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Metastatic Cancer ◽  
Intratumoral Injection
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