Cryopreservation of adenovirus-transfected dendritic cells (DCs) for clinical use

Gülen, Dumrul; Maas, Sarah A.; Julius, H. W.; Warkentin, Phyllis I.; Britton, Holly C.; Younos, Ibrahim; Senesac, J. H.; Pirruccello, Samuel J.; Talmadge, James E.

doi:10.1016/j.intimp.2012.03.009

Cited by 9 publications

(7 citation statements)

References 32 publications

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“…For this, efforts have been made to cryopreserve DC. Various reports using DC for cancer immunotherapy have demonstrated no differences regarding the morphology, phenotype, and function between cryopreserved and freshly generated DC [ 44 – 47 ]. However, to date, studies addressing the influence of cryopreservation on the characteristics of tolDC are limited.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we report the development and optimization of a cryopreservation protocol which yielded a recovery of 78% and a viability of 75% of immature 1,25(OH) 2 D 3 -treated DC following a freeze-thaw cycle. Previously, other studies investigating the effects of cryopreservation on immunostimulatory DC demonstrated a recovery of 86% on average [ 44 , 47 , 48 ]. In this study, the recovery of tolDC appears to be lower as compared to immunostimulatory DC, albeit not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory Effects of 1,25-Dihydroxyvitamin D₃on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Lee

Willekens

Cras

et al. 2016

Journal of Immunology Research

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While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment of monocyte-derived DC results in a semimature phenotype and anti-inflammatory cytokine profile as compared to conventional DC, in both healthy controls and MS patients. Importantly, 1,25(OH)2D3-treated DC induce T cell hyporesponsiveness, as demonstrated in an allogeneic mixed leukocyte reaction. Next, following a freeze-thaw cycle, 1,25(OH)2D3-treated immature DC could be recovered with a 78% yield and 75% viability. Cryopreservation did not affect the expression of membrane markers by 1,25(OH)2D3-treated DC nor their capacity to induce T cell hyporesponsiveness. In addition, the T cell hyporesponsiveness induced by 1,25(OH)2D3-treated DC is antigen-specific and robust since T cells retain their capacity to respond to an unrelated antigen and do not reactivate upon rechallenge with fully mature conventional DC, respectively. These observations underline the clinical potential of tolerogenic DC (tolDC) to correct the immunological imbalance in MS. Furthermore, the feasibility to cryopreserve highly potent tolDC will, ultimately, contribute to the large-scale production and the widely applicable use of tolDC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D₃on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Lee

Willekens

Cras

et al. 2016

Journal of Immunology Research

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“…Gü len et al showed that dendritic cells transduced with an adenovirus vector containing an interleukin-12 transgene may be cryopreserved with little effect on cell viability and transgene expression. 46 Li et al showed that cord blood myeloid progenitor cells can be transduced with a retroviral vector containing a neomycin resistance gene after cryopreservation, and that transduced cells successfully recovered gene expression after cyropreservation. 47 The present results differ in that ASCs transduced prior to cryopreservation had diminished osteogenic potential and a trend toward decreased BMP-2 production.…”

Section: Discussionmentioning

confidence: 99%

Cryopreservation of Human Adipose-Derived Stem Cells for Use in Ex Vivo Regional Gene Therapy for Bone Repair

Vakhshori

Bougioukli

Sugiyama

et al. 2018

Human Gene Therapy Methods

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The development of an ex vivo regional gene therapy clinical pathway using adipose-derived stem cells (ASCs) may require cryopreservation for cell culture, storage, and transport prior to clinical use. ASCs isolated from five donors were transduced with a lentiviral vector containing BMP-2. Three groups were assessed: transduction without cell freezing (group 1), freezing of cells for 3 weeks followed by transduction (group 2), and cell transduction prior to freezing (group 3). Nontransduced cells were used as a control. The cluster of differentiation (CD) marker profiles, cell number, BMP-2 production, and osteogenic potential were measured. The CD marker profile (CD44, CD73, CD90, and CD105) was unchanged after cryopreservation. Cell number was equivalent among cryopreservation protocols in transduced and nontransduced cells. There was a trend toward decreased BMP-2 production in group 3 compared to groups 1 and 2. Osteogenic potential based on Alizarin red concentration was higher in group 2 compared to group 3, with no difference compared to group 1. Freezing ASCs prior to transduction with a lentiviral vector containing BMP-2 has no detrimental effect on cell number, BMP-2 production, osteogenic potential, or immunophenotype. Transduction prior to freezing, however, may limit the BMP-2 production and potential osteogenic differentiation of the ASCs.

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“…In addition, newly formed HLA complex remained stable after freezing and thawing the transduced cells, a method used by some authors to ensure the stability of transgene expression. 33,34 Expression of the functional HLA class I complex on the cell surface requires coordinated participation of multiple proteins, which are part of APM, including TAP1/2, tapasin, calnexin, calreticulin, LMP2/7 and Erp57. They process HLA antigens in the ER, control correct folding of the heavy chain, its association with b2m and correct transport of this complex to the cell surface via Golgi apparatus.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus expressing β2-microglobulin recovers HLA class I expression and antitumor immunity by increasing T-cell recognition

et al. 2014

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Optimal tumor cell surface expression of human leukocyte antigen (HLA) class I molecules is essential for the presentation of tumor-associated peptides to T-lymphocytes. However, a hallmark of many types of tumor is the loss or downregulation of HLA class I expression associated with ineffective tumor antigen presentation to T cells. Frequently, HLA loss can be caused by structural alterations in genes coding for HLA class I complex, including the light chain of the complex, β2-microglobulin (β2m). Its best-characterized function is to interact with HLA heavy chain and stabilize the complex leading to a formation of antigen-binding cleft recognized by T-cell receptor on CD8+ T cells. Our previous study demonstrated that alterations in the β2m gene are frequently associated with cancer immune escape leading to metastatic progression and resistance to immunotherapy. These types of defects require genetic transfer strategies to recover normal expression of HLA genes. Here we characterize a replication-deficient adenoviral vector carrying human β2m gene, which is efficient in recovering proper tumor cell surface HLA class I expression in β2m-negative tumor cells without compromising the antigen presentation machinery. Tumor cells transduced with β2m induced strong activation of T cells in a peptide-specific HLA-restricted manner. Gene therapy using recombinant adenoviral vectors encoding HLA genes increases tumor antigen presentation and represents a powerful tool for modulation of tumor cell immunogenicity by restoration of missing or altered HLA genes. It should be considered as part of cancer treatment in combination with immunotherapy.

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Cryopreservation of adenovirus-transfected dendritic cells (DCs) for clinical use

Cited by 9 publications

References 32 publications

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D₃on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D₃on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Cryopreservation of Human Adipose-Derived Stem Cells for Use in Ex Vivo Regional Gene Therapy for Bone Repair

Adenovirus expressing β2-microglobulin recovers HLA class I expression and antitumor immunity by increasing T-cell recognition

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Cryopreservation of adenovirus-transfected dendritic cells (DCs) for clinical use

Cited by 9 publications

References 32 publications

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D3on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D3on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Cryopreservation of Human Adipose-Derived Stem Cells for Use in Ex Vivo Regional Gene Therapy for Bone Repair

Adenovirus expressing β2-microglobulin recovers HLA class I expression and antitumor immunity by increasing T-cell recognition

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Product

Resources

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Immunomodulatory Effects of 1,25-Dihydroxyvitamin D₃on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D₃on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens