共查询到20条相似文献,搜索用时 15 毫秒
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Zahra Payandeh Maral Yarahmadi Ziba Nariman-Saleh-Fam Vahideh Tarhriz Maryam Islami Abdolreza Mehdinavaz Aghdam Shirin Eyvazi 《Journal of cellular physiology》2019,234(9):14612-14621
Melanoma is the most serious type of skin cancer which develops from the occurrence of genetic mutations in the melanocytes. Based on the features of melanoma tumors such as location, genetic profile and stage, there are several therapeutic strategies including surgery, chemotherapy, and radiotherapy. However, because of the appearance resistance mechanisms, the efficiency of these treatments strategies may be reduced. It has been demonstrated that therapeutic monoclonal antibodies can improve the efficiency of melanoma therapies. Recently, several mAbs, such as nivolumab, pembrolizumab, and ipilimumab, were approved for the immunotherapy of melanoma. The antibodies inhibit immune checkpoint receptors such as CTL4 and pd-1. Another therapeutic strategy for the treatment of melanoma is cancer vaccines, which improve clinical outcomes in patients. The combination therapy using antibodies and gene vaccine give us a new perspective in the treatment of melanoma patients. Herein, we present the recent progressions in the melanoma immunotherapy, especially dendritic cells mRNA vaccines by reviewing recent literature. 相似文献
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Chimeric antigen receptor (CAR) T-cells are redirected T-cells that can recognize cancer antigens in a major histocompatibility complex (MHC)-independent fashion. A typical CAR is comprised of two main functional domains: an extracellular antigen recognition domain, called a single-chain variable fragment (scFv), and an intracellular signaling domain. Based on the number of intracellular signaling molecules, CARs are categorized into four generations. CAR T-cell therapy has become a promising treatment for hematologic malignancies. However, results of its clinical trials on solid tumors have not been encouraging. Here, we described the structure of CARs and summarized the clinical trials of CD19-targeted CAR T-cells. The side effects, safety management, challenges, and future prospects of CAR T-cells for the treatment of cancer, particularly for solid tumors, were also discussed. 相似文献
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Chih-Chun Wen Hui-Ming Chen Swey-Shen Chen Li-Ting Huang Wei-Ting Chang Wen-Chi Wei Li-Chen Chou Palanisamy Arulselvan Jin-Bin Wu Sheng-Chu Kuo Ning-Sun Yang 《Journal of biomedical science》2011,18(1):1-15
Background
Damage-associated molecular patterns (DAMPs) are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs). Specific microtubule-depolymerizing agents (MDAs) such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs.Methods
In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues) to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine.Results
The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT). DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs.Conclusions
Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs) can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine. 相似文献6.
Jenny Bulgarelli Laura Fiammenghi Serena Cassan Anna Maria Granato Massimiliano Petrini Elena Pancisi Valentina Soldati Francesco De Rosa Laura Ridolfi Angela Riccobon Massimo Guidoboni 《Cytotherapy》2018,20(6):851-860
Background
Dendritic cells (DCs) are the most efficient antigen-presenting cells and act at the center of the immune system owing to their ability to control both immune tolerance and immunity. In cancer immunotherapy, DCs play a key role in the regulation of the immune response against tumors and can be generated ex vivo with different cytokine cocktails. Methods. We evaluated the feasibility of dinoprostone (PGE2) replacement with the molecular analog sulprostone, in our good manufacturing practice (GMP) protocol for the generation of DC-based cancer vaccine. We characterized the phenotype and the function of DCs matured in the presence of sulprostone as a potential substitute of dinoprostone in the pro-inflammatory maturation cocktail consisting of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6. Results. We found that sulprostone invariably reduces the recovery, but does not significantly modify the viability and the purity of DCs. The presence of sulprostone in the maturation cocktail increases the adhesion of single cells and of clusters of DCs to the flask, making them more similar to their immature counterpart in terms of adhesion and spreading proprieties. Moreover, we observed that sulprostone impairs the expression of co-stimulatory molecules and the spontaneous as well as the directed migration capacity of DCs.Discussion
These findings underscore that the synthetic analog sulprostone strongly reduces the functional quality of DCs, thus cannot replace dinoprostone in the maturation cocktail of monocyte-derived DCs. 相似文献7.
Jashodeep Datta Julia H. Terhune Lea Lowenfeld Jessica A. Cintolo Shuwen Xu Robert E. Roses Brian J. Czerniecki 《The Yale journal of biology and medicine》2014,87(4):491-518
Dendritic cells (DC) are professional antigen-presenting cells uniquely suited for cancer immunotherapy. They induce primary immune responses, potentiate the effector functions of previously primed T-lymphocytes, and orchestrate communication between innate and adaptive immunity. The remarkable diversity of cytokine activation regimens, DC maturation states, and antigen-loading strategies employed in current DC-based vaccine design reflect an evolving, but incomplete, understanding of optimal DC immunobiology. In the clinical realm, existing DC-based cancer immunotherapy efforts have yielded encouraging but inconsistent results. Despite recent U.S. Federal and Drug Administration (FDA) approval of DC-based sipuleucel-T for metastatic castration-resistant prostate cancer, clinically effective DC immunotherapy as monotherapy for a majority of tumors remains a distant goal. Recent work has identified strategies that may allow for more potent “next-generation” DC vaccines. Additionally, multimodality approaches incorporating DC-based immunotherapy may improve clinical outcomes. 相似文献
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David Koos Doru T Alexandrescu Ray Chun-Fai Chan Vladimir Bogin Constantin A. Dasanu Neil H. Riordan 《Cellular immunology》2010,263(2):138-2616
Induction of tumor-specific immunity is an attractive approach to cancer therapy, however to date every major pivotal trial has resulted in failure. While the phenomena of tumor-mediated immune suppression has been known for decades, only recently have specific molecular pathways been elucidated, and for the first time, rationale means of intervening and observing results of intervention have been developed. In this review we describe major advances in our understanding of tumor escape from immunological pressure and provide some possible therapeutic scenarios for enhancement of efficacy in future cancer vaccine trials. 相似文献
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Ueda Y Itoh T Fuji N Harada S Fujiki H Shimizu K Shiozaki A Iwamoto A Shimizu T Mazda O Kimura T Sonoda Y Taniwaki M Yamagishi H 《Cancer immunology, immunotherapy : CII》2007,56(3):381-389
Recent studies have suggested that dendritic cell (DC)-based immunotherapy is one promising approach for the treatment of
cancer. We previously studied the clinical toxicity, feasibility, and efficacy of cancer vaccine therapy with peptide-pulsed
DCs. In that study, we used granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood monocytes as a cell source
of DCs. However, previous investigations have suggested that G-CSF-mobilized peripheral blood monocytes produce reduced levels
of proinflammatory cytokines such as interleukin (IL)-12 and tumor necrosis factor (TNF)-α. These T helper (Th)-1-type cytokines
are thought to promote antitumor immune response. In this study, we assessed the functional abilities of DCs generated from
G-CSF-mobilized monocytes obtained from 13 patients with CEA-positive advanced solid cancers. Peripheral blood mononuclear
cells were obtained from leukapheresis products collected before and after systemic administration of G-CSF (subcutaneous
administration of high-dose [5–10 μg/kg] human recombinant G-CSF for five consecutive days). In vitro cytokine production
profiles after stimulation with lipopolysaccharide (LPS) were compared between monocytes with and without G-CSF mobilization.
DCs generated from monocytes were also examined with respect to cytokine production and the capacity to induce peptide-specific
T cell responses. Administration of G-CSF was found to efficiently mobilize peripheral blood monocytes. Although G-CSF-mobilized
monocytes (G/Mo) less effectively produced Th-1-type cytokines than control monocytes (C/Mo), DCs generated from G/Mo restored
the same level of IL-12 production as that seen in DCs generated from C/Mo. T cell induction assay using recall antigen peptide
and phenotypic analyses also demonstrated that DCs generated from G/Mo retained characteristics identical to those generated
from C/Mo. Our results suggest that G-CSF mobilization can be used to collect monocytes as a cell source for the generation
of DCs for cancer immunotherapy. DCs generated in this fashion were pulsed with HLA-A24-restricted CEA epitope peptide and
administered to patients safely; immunological responses were induced in some patients. 相似文献
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Dendritic cells: Potential role in cancer therapy 总被引:2,自引:0,他引:2
Edgar G. Engleman 《Cytotechnology》1997,25(1-3):1-8
Dendritic cells (DC) are extremely potent antigen presenting cells, uniquely capable of sensitizing naive T cells to protein
antigens and eliciting antigen specific immune responses. Studies of human DC isolated from peripheral blood indicate that
these cells can be used to stimulate and expand antigen specific CD4+ and CD8+ T cells, in vitro. On the basis of these findings
we have initiated pilot clinical studies to investigate the ability of DC pulsed ex vivo with tumor associated proteins to
stimulate host anti-tumor immunity when re-infused as a vaccine. In the first such study DC pulsed with tumor derived idiotype
protein were infused into patients with low grade malignant B cell lymphoma who had failed conventional chemotherapy. The
majority of treated patients developed T cell mediated anti-idiotype immune responses and some of the patients experienced
tumor regression. These results suggest that DC based immunotherapy is a potentially useful approach to B cell lymphoma and
raises the possibility that the approach may prove useful in the treatment of other tumors as well.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
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Ogasawara K 《Microbiology and immunology》1999,43(10):915-923
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CONG CHEN YIN-HUA MA YA-TING ZHANG FAN ZHANG NING ZHOU XIANG WANG TAO LIU YU-MIN LI 《Cytotherapy》2018,20(8):975-989
Background aims
Dendritic cell (DC)-based immunotherapy has recently been reported frequently in the treatment of hepatocellular carcinoma (HCC); however, its efficacy remains controversial. In this study, we aimed to evaluate the clinical efficacy of DC-based immunotherapy on HCC by conducting a systematic review and meta-analysis.Methods
PubMed, Cochrane Library, Embase and Web of Science were searched to identify clinical trials on DC-based immunotherapy for HCC published up to January 31, 2018. The articles were selected according to pre-established inclusion criteria and methodologic quality, and publication bias were evaluated.Results
A total of 1276 cases from 19 clinical trials were included. Compared with traditional treatment, further DC-based therapy enhanced the CD4+ T/CD8+ T ratio (standardized mean difference: 0.68, 95% confidence interval [CI] 0.46–0.89, P < 0.001); increased the 1-year, 18-month and 5-year progression-free survival (PFS) rate and the 1-year, 18-month and 2-year overall survival (OS) rate (relative risk > 1, P < 0.05), prolonged the median PFS time (median survival ratio [MSR]: 1.98, 95% CI: 1.60–2.46, P < 0.001) and median OS time (MSR: 1.72, 95% CI: 1.51–1.96, P < 0.001). Adverse reactions were mild.Conclusions
DC-based therapy not only enhanced anti-tumor immunity, improved the survival rate and prolonged the survival time of HCC patients, but it was also safe. These findings will provide encouraging information for further development of DC-based immunotherapy as an adjuvant treatment for HCC. However, the results must be interpreted with caution because of the small study numbers, publication bias and the various of study designs, pre-treatment and therapeutic processes of DCs. 相似文献14.
FATEMEH KHATAMI MONIREH TORABI-RAHVAR JAFAR KIANI MAHMOOD NADERI NASER AHMADBEIGI 《Cytotherapy》2018,20(10):1227-1237
Recent advances in immunotherapeutic modalities have profoundly changed the prospect of cancer treatment. These modalities mainly focus on modulating the immune response toward tumor cells by using monoclonal antibodies, cancer vaccines, adoptive cell transfer or combination of these methods. In the last few years, Iranian scientists have conducted several projects in these arenas. Here, we provide an overview of these studies and analyze the quality and trend of publications in each sub-specialty of the field. In addition, the contribution of different universities and scientific institutes is assessed. This study may benefit scientific community and policymakers to plan future cancer immunotherapies in Iran and other countries. 相似文献
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Dendritic cells (DCs) are bone marrow–derived immune cells that play a crucial role in inducing the adaptive immunity and supporting the innate immune response independently from T cells. In the last decade, DCs have become a hopeful instrument for cancer vaccines that aims at re-educating the immune system, leading to a potent anti-cancer immune response able to overcome the immunosuppressive tumor microenvironment (TME). Although several studies have indicated that DC-based vaccines are feasible and safe, the clinical advantages of DC vaccination as monotherapy for most of the neoplasms remain a distant target. Recently, many reports and clinical trials have widely used innovative combinatorial therapeutic strategies to normalize the immune function in the TME and synergistically enhance DC function. This review will describe the most relevant and updated evidence of the anti-cancer combinatorial approaches to boost the clinical potency of DC-based vaccines. 相似文献
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Fotin-Mleczek M Zanzinger K Heidenreich R Lorenz C Thess A Duchardt KM Kallen KJ 《The journal of gene medicine》2012,14(6):428-439
Direct vaccination with mRNA encoding tumor antigens is a novel and promising approach in cancer immunotherapy. CureVac's mRNA vaccines contain free and protamine-complexed mRNA. Such two-component mRNA vaccines support both antigen expression and immune stimulation. These self-adjuvanting RNA vaccines, administered intradermally without any additional adjuvant, induce a comprehensive balanced immune response, comprising antigen specific CD4+ T cells, CD8+ T cells and B cells. The balanced immune response results in a strong anti-tumor effect and complete protection against antigen positive tumor cells. This tumor inhibition elicited by mRNA vaccines is a result of the concerted action of different players. After just two intradermal vaccinations, we observe multiple changes at the tumor site, including the up-regulation of many genes connected to T and natural killer cell activation, as well as genes responsible for improved infiltration of immune cells into the tumor via chemotaxis. The two-component mRNA vaccines induce a very fast and boostable immune response. Therefore, the vaccination schedules can be adjusted to suit the clinical situation. Moreover, by combining the mRNA vaccines with therapies in clinical use (chemotherapy or anti-CTLA-4 antibody therapy), an even more effective anti-tumor response can be elicited. The first clinical data obtained from two separate Phase I/IIa trials conducted in PCA (prostate cancer) and NSCLC (non-small cell lung carcinoma) patients have shown that the two-component mRNA vaccines are safe, well tolerated and highly immunogenic in humans. 相似文献
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Dohnal AM Graffi S Witt V Eichstill C Wagner D Ul-Haq S Wimmer D Felzmann T 《Journal of cellular and molecular medicine》2009,13(1):125-135
Manufacturing procedures for cellular therapies are continuously improved with particular emphasis on product safety. We previously developed a dendritic cell (DC) cancer vaccine technology platform that uses clinical grade lipopolysaccharide (LPS) and interferon (IFN)-y for the maturation of monocyte derived DCs. DCs are frozen after 6 hrs exposure at a semi-mature stage (smDCs) retaining the capacity to secret interleukin (IL)-12 and thus support cytolytic T-cell responses, which is lost at full maturation. We compared closed systems for monocyte enrichment from leucocyte apheresis products from healthy individuals using plastic adherence, CD14 selection, or CD2/19 depletion with magnetic beads, or counter flow centrifugation (elutriation) using a clinical grade in comparison to a research grade culture medium for the following DC generation. We found that elutriation was superior compared to the other methods showing 36 ± 4% recovery, which was approximately 5-fold higher as the most frequently used adherence protocol (8 ± 1%), and a very good purity (92 ± 5%) of smDCs. Immune phenotype and IL-12 secretion (adherence: 1.4 ± 0.4; selection: 20 ± 0.6; depletion: 1 ±0.5; elutriation: 3.6 ± 1.5 ng/ml) as well as the potency of all DCs to stimulate T cells in an allogeneic mixed leucocyte reaction did not show statistically significant differences. Research grade and clinical grade DC culture media were equally potent and freezing did not impair the functions of smDCs. Finally, we assessed the functional capacity of DC cancer vaccines manufactured for three patients using this optimized procedure thereby demonstrating the feasibility of manufacturing DC cancer vaccines that secret IL-12 (9.4 ± 6.4 ng/ml). We conclude that significant steps were taken here towards clinical grade DC cancer vaccine manufacturing. 相似文献