scholarly journals Cellular Immunotherapy Using Dendritic Cells Against Multiple Myeloma

10.5772/30646 ◽  
2012 ◽  
Author(s):  
Je-Jung Lee ◽  
Youn-Kyung Lee ◽  
Thanh-Nhan Nguyen-Pham
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Cellular Immunotherapy

scholarly journals Cellular Immunotherapy Using Dendritic Cells in Multiple Myeloma: New Concept to Enhance Efficacy

10.5772/54100 ◽  
2013 ◽  
Author(s):  
Je-Jung Lee ◽  
Youn-Kyung Lee ◽  
Hyun Ju ◽  
Sung-Hoon Jung ◽  
Thanh-Nhan Nguyen-Pham
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Cellular Immunotherapy

scholarly journals Immunotherapy Using Dendritic Cells against Multiple Myeloma: How to Improve?

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Thanh-Nhan Nguyen-Pham ◽  
Yoon-Kyung Lee ◽  
Hyeoung-Joon Kim ◽  
Je-Jung Lee
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Myeloma Cell ◽  
Cellular Immunotherapy ◽  
Immune Effector ◽  
Effector Cells ◽  
Good Target ◽  
Target Disease ◽  
Antigen Presenting ◽  
Dying Cells

Multiple myeloma (MM) is a good target disease in which one can apply cellular immunotherapy, which is based on the graft-versus-myeloma effect. This role of immune effector cells provides the framework for the development of immune-based therapeutic options that use antigen-presenting cells (APCs) with increased potency, such as dendritic cells (DCs), in MM. Current isolated idiotype (Id), myeloma cell lysates, myeloma dying cells, DC-myeloma hybrids, or DC transfected with tumor-derived RNA has been used for immunotherapy with DCs. Immunological inhibitory cytokines, such as TGF-β, IL-10, IL-6 and VEGF, which are produced from myeloma cells, can modulate antitumor host immune response, including the abrogation of DC function, by constitutive activation of STAT3. Therefore, even the immune responses have been observed in clinical trials, the clinical response was rarely improved following DC vaccinations in MM patients. We are going to discuss how to improve the efficacy of DC vaccination in MM.

scholarly journals Cellular immunotherapy using dendritic cells against multiple myeloma

2012 ◽  
Vol 47 (1) ◽  
pp. 17 ◽  
Author(s):  
Thanh-Nhan Nguyen-Pham ◽  
Youn-Kyung Lee ◽  
Hyun-Ju Lee ◽  
Mi-Hyun Kim ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Cellular Immunotherapy

scholarly journals Thapsigargin-Stimulated LAD2 Human Mast Cell Line Is a Potent Cellular Adjuvant for the Maturation of Monocyte-Derived Dendritic Cells for Adoptive Cellular Immunotherapy

2021 ◽  
Vol 22 (8) ◽  
pp. 3978
Author(s):  
Pavla Taborska ◽  
Dmitry Stakheev ◽  
Jirina Bartunkova ◽  
Daniel Smrz
Keyword(s):  
Dendritic Cells ◽  
Mast Cell ◽  
Ex Vivo ◽  
Human Leukocyte ◽  
Poly I:C ◽  
Human Mast Cell ◽  
Cellular Immunotherapy ◽  
Adoptive Cellular Immunotherapy ◽  
Serum Free ◽  
Dc Maturation

The preparation of dendritic cells (DCs) for adoptive cellular immunotherapy (ACI) requires the maturation of ex vivo-produced immature(i) DCs. This maturation ensures that the antigen presentation triggers an immune response towards the antigen-expressing cells. Although there is a large number of maturation agents capable of inducing strong DC maturation, there is still only a very limited number of these agents approved for use in the production of DCs for ACI. In seeking novel DC maturation agents, we used differentially activated human mast cell (MC) line LAD2 as a cellular adjuvant to elicit or modulate the maturation of ex vivo-produced monocyte-derived iDCs. We found that co-culture of iDCs with differentially activated LAD2 MCs in serum-containing media significantly modulated polyinosinic:polycytidylic acid (poly I:C)-elicited DC maturation as determined through the surface expression of the maturation markers CD80, CD83, CD86, and human leukocyte antigen(HLA)-DR. Once iDCs were generated in serum-free conditions, they became refractory to the maturation with poly I:C, and the LAD2 MC modulatory potential was minimized. However, the maturation-refractory phenotype of the serum-free generated iDCs was largely overcome by co-culture with thapsigargin-stimulated LAD2 MCs. Our data suggest that differentially stimulated mast cells could be novel and highly potent cellular adjuvants for the maturation of DCs for ACI.

Generation of dendritic cells from CD14+ monocytes positively selected by immunomagnetic adsorption for multiple myeloma patients enrolled in a clinical trial of anti-idiotype vaccination

2003 ◽  
Vol 121 (2) ◽  
pp. 240-250 ◽  
Author(s):  
Maria R. Motta ◽  
Samantha Castellani ◽  
Simonetta Rizzi ◽  
Antonio Curti ◽  
Francesco Gubinelli ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Dendritic Cells

Dendritic Cells and Peptide-Based Vaccine In Multiple Myeloma

2012 ◽  
pp. 131-154 ◽  
Author(s):  
Jooeun Bae ◽  
R. H. Prabhala ◽  
Nikhil C. Munshi
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells

scholarly journals Novel Strategies for Immunotherapy in Multiple Myeloma: Previous Experience and Future Directions

2012 ◽  
Vol 2012 ◽  
pp. 1-28 ◽  
Author(s):  
Ivetta Danylesko ◽  
Katia Beider ◽  
Avichai Shimoni ◽  
Arnon Nagler
Keyword(s):  
Multiple Myeloma ◽  
Specific Antigen ◽  
Allogeneic Transplantation ◽  
Cellular Immunotherapy ◽  
Future Directions ◽  
Study Protocols ◽  
Immune Incompetence ◽  
Life Threatening ◽  
Dc Vaccines ◽  
Antigen Presenting

Multiple myeloma (MM) is a life-threatening haematological malignancy for which standard therapy is inadequate. Autologous stem cell transplantation is a relatively effective treatment, but residual malignant sites may cause relapse. Allogeneic transplantation may result in durable responses due to antitumour immunity mediated by donor lymphocytes. However, morbidity and mortality related to graft-versus-host disease remain a challenge. Recent advances in understanding the interaction between the immune system of the patient and the malignant cells are influencing the design of clinically more efficient study protocols for MM. Cellular immunotherapy using specific antigen-presenting cells (APCs), to overcome aspects of immune incompetence in MM patients, has received great attention, and numerous clinical trials have evaluated the potential for dendritic cell (DC) vaccines as a novel immunotherapeutic approach. This paper will summarize the data investigating aspects of immunity concerning MM, immunotherapy for patients with MM, and strategies, on the way, to target the plasma cell more selectively. We also include the MM antigens and their specific antibodies that are of potential use for MM humoral immunotherapy, because they have demonstrated the most promising preclinical results.

Multiple myeloma–reactive T cells recognize an activation-induced minor histocompatibility antigen encoded by the ATP-dependent interferon-responsive (ADIR) gene

Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 4089-4096 ◽  
Author(s):  
Cornelis A. M. van Bergen ◽  
Michel G. D. Kester ◽  
Inge Jedema ◽  
Mirjam H. M. Heemskerk ◽  
Simone A. P. van Luxemburg-Heijs ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Cell Types ◽  
Donor Lymphocyte Infusion ◽  
Cellular Immunotherapy ◽  
Cell Reactivity ◽  
Cellular Activation ◽  
Minor Histocompatibility Antigens ◽  
Suitable Target ◽  
T Cell Reactivity

Abstract Minor histocompatibility antigens (mHags) play an important role in both graft-versus-tumor effects and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. We applied biochemical techniques and mass spectrometry to identify the peptide recognized by a dominant tumor-reactive donor T-cell reactivity isolated from a patient with relapsed multiple myeloma who underwent transplantation and entered complete remission after donor lymphocyte infusion. A frequently occurring single nucleotide polymorphism in the human ATP-dependent interferon-responsive (ADIR) gene was found to encode the epitope we designated LB-ADIR-1F. Although gene expression could be found in cells from hematopoietic as well as nonhematopoietic tissues, the patient suffered from only mild acute GVHD despite high percentages of circulating LB-ADIR-1F–specific T cells. Differential recognition of nonhematopoietic cell types and resting hematopoietic cells as compared with activated B cells, T cells, and tumor cells was demonstrated, illustrating variable LB-ADIR-1F expression depending on the cellular activation state. In conclusion, the novel mHag LB-ADIR-1F may be a suitable target for cellular immunotherapy when applied under controlled circumstances.

scholarly journals Clinical-Grade Functional Dendritic Cells From Patients With Multiple Myeloma Are Not Infected With Kaposi's Sarcoma-Associated Herpesvirus

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 1852-1857 ◽  
Author(s):  
Karin Tarte ◽  
Sonja J. Olsen ◽  
Zhao Yang Lu ◽  
Eric Legouffe ◽  
Jean-François Rossi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Kaposi's Sarcoma ◽  
Fluorescein Isothiocyanate ◽  
Kaposi’S Sarcoma ◽  
Interleukin 4 ◽  
Clinical Grade ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Abstract Bone marrow dendritic cells (DC) from patients with multiple myeloma (MM) were recently reported to be infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Because immunotherapy strategies using DC are very promising in this disease, we looked for KSHV DNA in clinical-grade DC generated in vitro from MM patients. Adherent apheresis cells from MM patients were maintained for 7 days in clinical-grade X-VIVO 15 culture medium supplemented with granulocyte-macrophage colony-stimulating factor, interleukin-4, or interleukin-13. Tumor necrosis factor α was added for the last 2 days. We obtained a cell population with a DC phenotype able to endocytose fluorescein isothiocyanate (FITC)-dextran and efficiently activate resting allogenic T lymphocytes. To detect KSHV DNA, we used polymerase chain reaction (PCR) followed by Southern blotting of PCR product with a sensitivity detecting a few copies of viral DNA. All the PCR were repeated in a blinded fashion three times, on 1 μg and 0.2 μg of genomic DNA, in two different laboratories. Clinical-grade DC from 10 (91%) of 11 patients were not infected with KSHV. The apheresis cells and the purified CD34+ cells from the same patients were also negative. A very weak PCR band was detected with DC from one patient, but the initial apheresis cells were negative. The detection of KSHV infection in 1 (9%) of 11 MM patients probably represents background seroprevalence. It seems likely that functional and clinical-grade DC from MM patients can safely be used in clinical trials.

scholarly journals Cytolytic Activity of Effector T-lymphocytes Against Hepatocellular Carcinoma is Improved by Dendritic Cells Pulsed with Pooled Tumor Antigens

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Thaweesak Chieochansin ◽  
Chutamas Thepmalee ◽  
Janya Grainok ◽  
Mutita Junking ◽  
Pa-thai Yenchitsomanus
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cell Lines ◽  
Cytolytic Activity ◽  
Cellular Immunotherapy ◽  
High Recurrence Rate ◽  
Target Cells ◽  
Lymphocyte Function ◽  
Cell Lysate

AbstractCellular immunotherapy is a promising new therapeutic approach for hepatocellular carcinoma (HCC), which has a high recurrence rate, irrespective of the treatment administered. In this study, we attempted to improve the cytolytic activity of effector T-lymphocytes against HCC. T-lymphocytes were activated by monocyte-derived dendritic cells (DCs) pulsed with cell lysate or RNA prepared from HCC cell lines. Monocytes were activated for differentiation into DCs by treatment with the IL4 and GM-CSF. DCs were pulsed with cell lysate or RNA prepared from a single cell line or combinations of two or three HCC cell lines, and then co-cultured with autologous T-lymphocytes with the intent of creating specific cytotoxicity. We discovered that DCs pulsed with total RNA effectuated greater T-lymphocyte function than DCs pulsed with total cell lysate, as evidenced by greater cytolytic activities against HCC target cells. The percentage of Huh7, HepG2, and SNU449 cell apoptosis at effector:target ratio of 10:1 was 42.6 ± 4.5% (p = 0.01), 33.6 ± 3.1% (p = 0.007), and 21.4 ± 1.4% (p < 0.001), respectively. DCs pulsed with pools of antigens prepared from three cell lines improved the cytolytic function of effector T-lymphocytes by approximately two-fold (p < 0.001), which suggests that this approach be further developed and applied for adoptive transfer treatment of HCC.

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