Dendritic cell vaccines for the treatment of prostate cancer

Lehrfeld, Todd J.; Lee, David I.

doi:10.1016/j.urolonc.2007.12.002

Cited by 7 publications

(3 citation statements)

References 48 publications

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“…DC vaccines have now been tested in numerous animal models and clinical trials. Positive results from animal models led to a large number of clinical trials, which have been planned and/or tested for many different types of tumors, including glioblastoma 1–3 , astrocytoma 4 melanoma 5, 6 , pancreatic 5, 7 , renal cell 8 colorectal 9 prostate, (reviewed in 10 ), hepatocellular 11 chronic lymphocytic leukemia 12, 13 medullary thyroid 14 , breast 15 ; and acute myelogenous leukemia 16 . Despite this potential and widespread use, many immunotherapies have not met with the degree of success that was hoped.…”

Section: Introductionmentioning

confidence: 99%

Induction of the glucocorticoid-induced leucine zipper gene limits the efficacy of dendritic cell vaccines

et al. 2011

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Dendritic cell (DC) vaccines have shown great promise in generating anti-tumor immune responses but have generally fallen short of producing durable cures. Determining mechanisms by which these vaccines fail will provide one strategy towards improving their success. Several manipulations of DCs have improved their migration and longevity, but the immune inhibitory environment surrounding tumors provides a powerful suppressive influence. To determine the mechanisms by which DCs at the site of the tumor convert to a suppressive phenotype, we evaluated pathways in DCs that become expressed at the tumor site. Our results revealed that tumors lead to induction of the glucocorticoid induced leucine zipper (GILZ) gene in DCs, and that this gene is critical for the development of tumor induced tolerance of both DCs and T cells. Previous data suggested that GILZ is a pivotal gene in the balance between activation and tolerance of DCs. Our new data show that GILZ is highly upregulated in DCs in the tumor microenvironment in vivo and that blockade of this gene in DC vaccines significantly improves long term survival. These results suggest that GILZ may be an ideal candidate gene to target for novel immune-based tumor therapies.

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Section: Introductionmentioning

confidence: 99%

Induction of the glucocorticoid-induced leucine zipper gene limits the efficacy of dendritic cell vaccines

et al. 2011

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“…Administration of autologous or allogeneic cytotoxic T lymphocytes, generated by co-stimulation with dendritic-tumor cell hybrids, tailored to present the putative tumor specific antigens for each individual patient, was already proven to be effective in other malignancies such as prostate cancer and melanoma, as well as in the treatment of post-transplant CMV infections [47][48][49].…”

Section: Discussionmentioning

confidence: 99%

HLA-Identical Dendritic-Leukemic Cell Hybrids Generate Specific CTLs in Vitro

Eshel¹,

Shpringer²,

Voskobinik³

et al. 2010

JCT

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hile being instrumental in the treatment of leukemic relapse after allogeneic hematopoietic stem cell transplantation, the impact of donor lymphocyte infusion (DLI) and its effectiveness remain debatable. Consequently it is widely accepted that more efforts are needed in order to make DLI more effective. This communication thus deals with the generation of specific CTLs in the clinical setting of HLA matched hematopoietic stem cell transplantation, to be used as an improved DLI treatment for post-transplantation relapsed leukemias. We assessed the potential of fused dendritic cells from donor origin, with leukemic cells from the HLA matched recipient for the generation of donor anti-tumor CTLs. Leukemic cells and donor dendritic cells were fused using polyethylene glycol (PEG). The hybrids were analyzed for double phenotype of both DC and tumor, and used for the education and generation of cytotoxic donor lymphocytes. Results demonstrate that efficient and specific CTLs can be generated and used in vitro for the elimination of the recipient tumor cells. These results form the basis for the establishment of a novel methodology aimed at generating active or passive anti-leukemic vaccine in relapsed patients

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“…By March 2010, almost 300 papers have been published reporting on 4422 patients treated (not all under Good Clinical Practice (GCP) conditions: primarily melanoma [32,33] and prostate cancer [34] patients -1301 and 510 patients, respectively). Most trials employed monocyte-derived DC (MoDC), which were most often generated from monocytes by culture in GM-CSF1IL-4 over approximately 6 days to obtain immature DC, followed by exposure to monocyte-conditioned medium or its mimic (cocktail composed of TNF-a1IL-1b1 IL-61PGE2) for 1-2 days, to yield ''cocktail''-matured DC.…”

Section: Adoptive Transfer Of Antigen-loaded DC Into Patients (Dc Vacmentioning

confidence: 99%

Dendritic cells in cancer immunotherapy

Schuler

2010

Eur J Immunol

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DC initiate and regulate T‐cell immunity and are thus the key to optimization of all types of vaccines. Insights into DC biology offer many opportunities to enhance immunogenicity. In this Viewpoint, I discuss some recent developments and findings that are of immediate relevance for the clinical development of cancer vaccines. In addition, I emphasize my personal view that we should explore the potential of adoptively transferred DC (i.e. DC vaccination) as cancer vaccines by performing two‐armed trials that address critical variables and by delivering antigens via mRNA‐transfected DC.

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Dendritic cell vaccines for the treatment of prostate cancer

Cited by 7 publications

References 48 publications

Induction of the glucocorticoid-induced leucine zipper gene limits the efficacy of dendritic cell vaccines

Induction of the glucocorticoid-induced leucine zipper gene limits the efficacy of dendritic cell vaccines

HLA-Identical Dendritic-Leukemic Cell Hybrids Generate Specific CTLs in Vitro

Dendritic cells in cancer immunotherapy

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