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101.
Katerina Vopenkova Klara Mollova Ivana Buresova Jaroslav Michalek 《Journal of cellular and molecular medicine》2012,16(11):2827-2837
Dendritic cell (DC) immunotherapy is capable of generating tumour‐specific immune responses. Different maturation strategies were previously tested to obtain DC capable of anti‐cancer responses in vitro, usually with limited clinical benefit. Mutual comparison of currently used maturation strategies and subsequent complex evaluation of DC functions and their stimulatory capacity on T cells was performed in this study to optimize the DC vaccination strategy for further clinical application. DC were generated from monocytes using granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and interleukin (IL)‐4, pulsed with whole tumour cell lysate and then matured with one of five selected maturation strategies or cultured without additional maturation stimulus. DC were characterized with regard to their surface marker expression, cytokine profiles, migratory capacity, allogeneic and autologous T cell stimulatory capacity as well as their specific cytotoxicity against tumour antigens. We were able to demonstrate extensive variability among different maturation strategies currently used in DC immunotherapeutic protocols that may at least partially explain limited clinical benefit of some clinical trials with such DC. We identified DC matured with interferon‐γ and lipopolysaccharide as the most attractive candidate for future clinical trials in cancer immunotherapy. 相似文献
102.
Fabio Moda Chiara Vimercati Ilaria Campagnani Margherita Ruggerone Giorgio Giaccone Michela Morbin Lorena Zentilin Mauro Giacca Ileana Zucca Giuseppe Legname Fabrizio Tagliavini 《朊病毒》2012,6(4):383-390
Prion diseases are caused by a conformational modification of the cellular prion protein (PrPC) into disease-specific forms, termed PrPSc, that have the ability to interact with PrPC promoting its conversion to PrPSc. In vitro studies demonstrated that anti-PrP antibodies inhibit this process. In particular, the single chain variable fragment D18 antibody (scFvD18) showed high efficiency in curing chronically prion-infected cells. This molecule binds the PrPC region involved in the interaction with PrPSc thus halting further prion formation. These findings prompted us to test the efficiency of scFvD18 in vivo. A recombinant Adeno-Associated Viral vector serotype 9 was used to deliver scFvD18 to the brain of mice that were subsequently infected by intraperitoneal route with the mouse-adapted scrapie strain RML. We found that the treatment was safe, prolonged the incubation time of scrapie-infected animals and decreased the burden of total proteinase-resistant PrPSc in the brain, suggesting that scFvD18 interferes with prion replication in vivo. This approach is relevant for designing new therapeutic strategies for prion diseases and other disorders characterized by protein misfolding. 相似文献
103.
Iida H Takayanagi K Nakanishi T Kume A Muramatsu K Kiyohara Y Akiyama Y Osaka T 《Biotechnology and bioengineering》2008,101(6):1123-1128
Preparation of human immune T cells containing iron-oxide nanoparticles was carried out for the development of magnetically mediated immunotherapy. Peripheral blood lymphocytes (PBLs) after the incubation with magnetite nanoparticles were found to contain measurable ferric ions, which suggested the incorporation of magnetite nanoparticles. Transmission electron microscopic (TEM) study indicated that the incorporation of magnetite nanoparticles was mediated by endocytosis of PBLs. Furthermore, the effects of dosages and diameter of magnetite nanoparticles on the magnetite incorporation were investigated, and it was demonstrated that the increase in dosage promoted the incorporation of nanoparticles and the uptake into PBLs was more effective for magnetite nanoparticles, which formed smaller aggregations in medium. Finally, the demonstration of magnetite incorporation into enriched T cells and tumor antigen-specific cytotoxic T lymphocyte (CTL) line promises the achievement of magnetically mediated immunotherapy with tumor-specific CTLs containing magnetic nanoparticles. 相似文献
104.
Labarrière N Gervois N Bonnin A Bouquié R Jotereau F Lang F 《Cancer immunology, immunotherapy : CII》2008,57(2):185-195
Choosing a reliable source of tumor-specific T lymphocytes and an efficient method to isolate these cells still remains a
critical issue in adoptive cellular therapy (ACT). In this study, we assessed the capacity of MHC/peptide based immunomagnetic
sorting followed by polyclonal T cell expansion to derive pure polyclonal and tumor-reactive Melan-A specific T cell populations
from melanoma patient’s PBMC and TIL. We first demonstrated that this approach was extremely efficient and reproducible. We
then used this procedure to compare PBMC and TIL-derived cells from three melanoma patients in terms of avidity for Melan-A
A27L analog, Melan-A26–35 and Melan-A27–35, tumor reactivity (lysis and cytokine production) and repertoire. Regardless of their origin, i.e., fresh PBMC, peptide stimulated
PBMC or TIL, all sorted populations (from the three patients) were cytotoxic against HLA-A2+ melanoma cell lines expressing
Melan-A. Although some variability in peptide avidity, lytic activity and cytokine production was observed between populations
of different origins in a given patient, it differed from one patient to another and thus no correlation could be drawn between
T cell source and reactivity. Analysis of Vβ usage within the sorted populations showed the recurrence of Vβ3 and Vβ14 subfamilies
in the three patients but differences in the rest of the Melan-A repertoire. In addition, in two patients, we observed major
repertoire differences between populations sorted from the three sources. We especially documented that in vitro peptide stimulation
of PBMC, used to facilitate the sort by enriching in specific T lymphocytes, could significantly alter their repertoire and
reactivity towards tumor cells. We conclude that PBMC which are easily obtained from all melanoma patients, can be as good
a source as TIL to derive high amounts of tumor-reactive Melan-A specific T cells, with this selection/amplification procedure.
However, the conditions of peptide stimulation should be improved to prevent a possible loss of reactive clonotypes.
Nathalie Labarrière and Nadine Gervois have equally contributed to this work. 相似文献
105.
Xie LH Sin FW Cheng SC Cheung YK Chan KT Xie Y Xie Y 《Cancer immunology, immunotherapy : CII》2008,57(7):1029-1038
Induction of anti-tumor immune responses by dendritic cells (DCs) transduced with a recombinant adeno-associated virus type
2 (rAAV2) encoding tumor antigens is considered a promising approach for cancer vaccine development. CML28, a novel antigen
with the properties of cancer/testis (CT) antigens, is an attractive target for antigen-specific immunotherapy. Here we investigated
the feasibility of inducing CML28-specific cytotoxic T lymphocyte (CTL) responses using DCs transduced with the rAAV2 vectors
containing the CML28 gene (rAAV/CML28). Using an adenovirus-free packaging system, rAAV/CML28 was generated. The transduction
efficiency of rAAV/CML28 in DCs increased in a multiplicity of infection (MOI)-dependent manner. The rAAV/CML28 transduction
did not impair DC maturation, but even enhanced the CD80 expression. The rAAV/CML28-transduced DCs induced CML28-specific
CTLs which exhibited a MHC class I-mediated antigen-specific lytic activity against CML28-bearing tumor cell lines (HepG2
and MCF-7) as well as the primary leukemia blasts. These findings suggest that rAAV/CML28-transduced DCs vaccine may serve
as a feasible approach for the treatment of CML28-associated cancers. 相似文献
106.
简要介绍了EB病毒的感染类型及机体对不同类型EB病毒感染的免疫反应,并对EB病毒相关疾病的免疫治疗手段和疫苗发展策略进行了评述。 相似文献
107.
Koji Kawai Hitoshi Hayashi Yoshinobu Ozaki Kaoru Saijo Shu Qin Liu Hideyuki Akaza Tadao Ohno 《Cytotechnology》2001,37(1):31-40
Adoptive immunotherapy with human cytotoxic T lymphocytes (CTL) is a promising cancer treatment. Previously we showed that
human CTLs against various types of tumors can be efficiently produced by coculturing peripheral blood cells with target cells.
The aims of this study were to simulate the interaction of CTLs and micrometer-size tumor tissues in vitro and to assess the required number of CTLs at local tumor sites for degradation of a tumor. Allogeneic CTLs against a human
transitional cell carcinoma cell line and autologous CTLs against a renal cell carcinoma cell derived from a surgical specimen
were generated. The cytotoxic activities of CTLs against tumor cells in monolayer culture and tumor spheroids formed in U-bottom
96-well culture plates were assessed. Both allogeneic and autologous CTLs showed greater destructive activity than lymphokine
activated killer (LAK) cells against target tumor spheroids. CTLs inoculated at E/T ratios of 0.1 to 1 coexisted with the
tumor spheroid for 5 to 6 days and then increased in number with apparently lethal activity against the tumor spheroid. In
contrast to CTLs, the increase in LAK cell numbers was scarcely observed, and the proliferated LAK cells did not show cytotoxicity
against the tumor spheroid. These observations suggest that, when a small number of CTLs reach a local tumor site, they can
destroy micrometer-size tumors after considerable local proliferation.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
108.
Jia Z. Shen Zhixin Qiu Qiulian Wu Darren Finlay Guillermina Garcia Dahui Sun Juha Rantala William Barshop Jennifer L. Hope Ryan C. Gimple Olle Sangfelt Linda M. Bradley James Wohlschlegel Jeremy N. Rich Charles Spruck 《Cell》2021,184(2):352-369.e23
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109.
《Developmental cell》2023,58(13):1170-1188.e7
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110.
《Bioorganic & medicinal chemistry letters》2020,30(9):127067
Adenosine pathway, including its generating enzyme (CD73) and its receptors represents a key target for cancer immunotherapy. Here we aimed to search for novel compounds able to co-target the CD73 and the A2A adenosine receptor (A2A AR) as dual-blockers of adenosine generation and activity. The design project was to combine in the same molecule the thiazolo[5,4-d]pyrimidine core, an essential pharmacophoric feature to block the A2A AR, with a benzenesulfonamide group which is a characteristic group of CD73 inhibitors. Most of the reported compounds resulted in inverse agonists of the human (h) A2A AR endowed with high affinity, selectivity and potency. However they were weak inhibitors of CD73 enzyme. Nevertheless, this study can be considered as a starting point to develop more active compounds. 相似文献