A method for the production of cryopreserved aliquots of antigen-preloaded, mature dendritic cells ready for clinical use

Feuerstein, Bernadette; Berger, Thomas G.; Maczek, Christian; Röder, Claudia; Schreiner, Doris; Hirsch, Ute; Haendle, Ina; Leisgang, Waltraud; Glaser, Anke; Kuß, Oliver; Diepgen, Thomas L.; Schuler, Gerold; Schuler‐Thurner, Beatrice

doi:10.1016/s0022-1759(00)00269-6

Cited by 144 publications

(96 citation statements)

References 32 publications

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“…Erin Mehlhop et al (17) compared the factors to induce human DC maturation, including MCM, CD40L, poly (I:C), LPS, PGE2/TNF-, cocktail of PGE2/TNF-/IL-1/IL-6 (CKT), CKT lacking IL-6 (CKT-6) or CKT lacking IL-1 (CKT-1β), to assessed the resultant changes using phenotypic and functional analyses. They found the CKT was the most consistent induction of mature macaque MDDC phenotype and function, just like the previous studies reported on the effectiveness of cytokine combinations for human DC maturation in FCS-free conditions (6,18). In the present study, we first chose LPS to stimulate the CRM MDDCs.…”

Section: Discussionsupporting

confidence: 57%

Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

et al. 2009

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Section: Discussionsupporting

confidence: 57%

Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

et al. 2009

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“…These offer the advantages of high yield, purity and feasibility, especially when leukapheresis is used to collect the starting monocytes. 111,112 It currently is feasible to obtain from patients with advanced melanoma 500 million mature DCs (current protocols use approx. 5 million DCs per vaccination).…”

Section: Sources and Subsets Of Dcsmentioning

confidence: 99%

“…It also may be feasible to cryopreserve the antigen-bearing mature cells, greatly facilitating vaccination and therapy. 111,112 DC maturation from CD34 ϩ progenitors also is being characterized. 115 A clinical study with CD34-derived DCs has shown immune and some clinical efficacy in the short term.…”

Section: Sources and Subsets Of Dcsmentioning

confidence: 99%

Active immunization against cancer with dendritic cells: The near future

2001

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DCs 1 are antigen-presenting cells that regulate several components of the immune system. The mature or terminal stage of DC development induces specific T-cell immunity and resistance to experimental tumors in vivo. However, DC maturation is induced by inflammatory and microbial stimuli, so it is unlikely that mature DCs normally present antigens from tumor cells in cancer patients. Accordingly, clinical studies have begun in which DCs are generated ex vivo, charged with tumor antigens, exposed to maturation stimuli and reinfused to immunize patients. This approach has the potential to control responses to cancer antigens in a specific and nontoxic manner, in both vaccination and therapeutic settings.DCs can mobilize several immune resistance mechanisms. These include CD8ϩ CTLs, CD4 ϩ helper T cells, NK and NKT cells. Each of these lymphocytes recognizes targets through a distinct mechanism and has the capacity to kill tumor cells and release valuable protective cytokines like IFN-␥. CD4 ϩ T cells also provide essential help for the expansion and maintenance of CD8 ϩ cytolytic cells, while NK and NKT cells can eliminate targets that dampen presentation on MHC class I to escape CTL recognition. The stimulation and concerted action of these classes of lymphocytes can now be studied directly in patients, using ex vivo-derived DCs.Several findings have emerged from studies of healthy volunteers who have been immunized with DCs charged with model antigens, KLH protein and influenza virus matrix peptide. Mature DCs elicit a polarized Th1 type of CD4 T-cell response, only a single injection being required. Vaccination with antigen-bearing DCs also markedly improves the functional affinity of CD8 ϩ T cells. These findings are important in the context of immunotherapy because Th1 cells are more efficient helper cells in experimental models of viral infection and tumors, while high-affinity CTLs should improve recognition of tumor-derived peptides. An important caution also has surfaced when DCs are not adequately differentiated. Immature DCs can silence adaptive T-cell responses, e.g., by inducing IL-10 -producing, T-reg cells.DC-based active immunization does not result in major shortterm toxicity in healthy subjects or cancer patients. Tumor-specific T-cell responses have been induced and detected in fresh blood specimens without the need for restimulation in vitro. However, the immune responses observed in the first protocols are still smaller than those seen naturally in acute viral infections. Occasional clinical regressions have been noted in these initial feasibility studies, particularly in melanomas, pediatric tumors, lymphomas, prostate cancers and renal cell cancers. This information, coupled with progress in DC biology, suggests many ways to improve the efficacy of this new therapy. Some relevant topics include antigen loading and DC maturation procedures, frequency and route of DC injection, efficiency of DC homing to lymphoid tissues and their longevity once there and the role of distinct DC subsets. A val...

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“…Also, it is up-regulated during bacterial and viral infection as well as trauma (Heinrich et al 2003). TNF-a, IL-1b, IL-6 and PGE 2 were supposed to be essential cytokines for in vitro maturation of DCs and their production of interferon (IFN)-c and IL-12 (Blanco et al 2008;Bohnenkamp and Noll 2003;Feuerstein et al 2000;Obermaier et al 2003). In addition, PGE 2 was able to induce the final maturation of IL-12-deficient CD1a…”

Section: Morphology Phenotype and Cd83mentioning

confidence: 99%

“…Therefore, most experimental and clinical trials currently rely on the in vitro development of DCs (Fong et al 2001). In traditional protocols, it is widely believed that the in vitro generation of mature DCs with full T cell stimulatory capacity from human monocytes (Mo) requires 5-7 days of differentiation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, followed by 2-3 days of maturation with proinflamatory cytokines and/or CD40 ligand (Bender et al 1996;Bohnenkamp and Noll 2003;Feuerstein et al 2000;Jonuleit et al 1997;Thurner et al 1999). However, there is increasing evidence that the time span required for DCs differentiation in vivo may be shorter.…”

Section: Introductionmentioning

confidence: 99%

Generation of functional monocyte-derived fast dendritic cells suitable for clinical application in the absence of interleukin-6

Ramadan

2011

Cytotechnology

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To develop dendritic cells (DCs)-based immunotherapy for cancer patients, it is necessary to have a standardized, reproducible, fast, and easy to use protocol for in vitro generation of fully functional DCs. Recently, a new strategy was described for differentiation and maturation of human monocyte (Mo)-derived fast-DCs with full T cell stimulatory capacity within only 48-72 h of in vitro culture. Interleukin (IL)-6 plus tumour necrosis factor (TNF)-a, IL-1b, and prostaglandin (PG)-E 2 were used in this strategy to induce maturation of the generated DCs. The present study further modifies this strategy by excluding IL-6 from the cytokines cocktail used for DCs maturation. The results showed that maturation of fast-DCs without IL-6 did not significantly alter the morphology, phenotype and the yield of mature DCs (P [ 0.05, compared with those generated with IL-6). Moreover, fast-DCs generated without IL-6 are functional antigen presenting cells, have the ability to induce tetanus toxoid-specific autologous T cell proliferation, and are suitable for gene delivery through adenoviral vector transduction as those generated with IL-6 (P [ 0.05). In conclusion, the present study proves that fully mature and functional Mo-derived fast-DCs can be generated in vitro without adding IL-6, which not only reduces the number of required recombinant cytokines, but may also resemble DCs development in vivo more closely.

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A method for the production of cryopreserved aliquots of antigen-preloaded, mature dendritic cells ready for clinical use

Cited by 144 publications

References 32 publications

Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

Active immunization against cancer with dendritic cells: The near future

Generation of functional monocyte-derived fast dendritic cells suitable for clinical application in the absence of interleukin-6

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