A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression

Euw, Erika M. Von; Barrio, María Marcela; Furman, David; Levy, Estrella Mariel; Bianchini, Michele; Péguillet, Isabelle; Lantz, Olivier; Vellice, Alejandra; Kohan, Abraham I.; Chacón, Matías; Yee, Cassian; Wainstok, Rosa; Mordoh, José

doi:10.1186/1479-5876-6-6

Cited by 54 publications

(45 citation statements)

References 52 publications

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“…Cellular immunotherapy using allogeneic tumor cells has been found to have a good safety profile (2,3) and in some studies where DCs are targeted, generated a CTL response (43,44). Several platforms using modified allogeneic cells have been introduced.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with Antigen-Transfected, NKT Cell Ligand–Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells

et al. 2013

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Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with cancer patients have yet to be developed. In murine models, a-galactosylceramide (a-GalCer)-loaded, tumor antigen-expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the innate and adaptive immune systems. In the current study, we established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the natural killer T (NKT) immune cell receptor CD1d, loaded with the CD1d ligand a-GalCer and then transfected with antigen-encoding mRNA. When administered to mice or dogs, these aAVC-activated invariant NKT (iNKT) cells elicited antigen-specific T-cell responses with no adverse events. In parallel experiments, using NOD/SCID/IL-2rgc null -immunodeficient (hDC-NOG) mouse model, we also showed that the human melanoma antigen, MART-1, expressed by mRNA transfected aAVCs can be cross-presented to antigenspecific T cells by human dendritic cells. Antigen-specific T-cell responses elicited and expanded by aAVCs were verified as functional in tumor immunity. Our results support the clinical development of aAVCs to harness innate and adaptive immunity for effective cancer immunotherapy. Cancer Res; 73(1); 62-73. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

Vaccination with Antigen-Transfected, NKT Cell Ligand–Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells

et al. 2013

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“…20,32,33 Indeed, this is in line with most other publications regarding IL-10 polymorphisms and melanoma. [22][23][24][26][27][28] In contrast, Nagano et al 34 reported that 'low-expression' IL-10 polymorphisms significantly protected from non-melanoma skin cancer. This may indicate that the effects of IL-10 differ in different skin cancer entities.…”

Section: Methodsmentioning

confidence: 98%

“…In addition, this genotype was a risk factor for poor disease outcome. In contrast, Liu et al 25 reported that the IL-10 À1087AA lowexpression genotype was associated with a longer survival in metastasized melanoma patients, whereas von Euw et al 28 found an accelerated tumour progression in AA genotypes. Alonso et al 26 reported no association of the IL-10 À1087AG , IL-10 À824CT and IL-10 À597AC polymorphisms with melanoma susceptibility; however, once again, decreased survival was observed in patients with the IL-10 À1087AA genotype.…”

Section: Introductionmentioning

confidence: 92%

“…Only seven studies investigated the role of proximal IL-10 promoter polymorphisms in melanoma susceptibility and in the course of metastasized melanoma. [22][23][24][25][26][27][28] Martinez-Escribano et al 22 found that the abovementioned proximal IL-10 promoter genotypes (SNPs IL-10 À1087AG , IL-10 À824CT and IL-10 À597AC ) were not associated with melanoma susceptibility. However, IL-10 low-producing haplotypes like ACC/ATA were associated with a shorter survival time and greater tumour thickness.…”

Section: Introductionmentioning

confidence: 99%

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Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

Schoof

Bonin

König³

et al. 2009

Genes Immun

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“…Several in vivo and clinical trials have been conducted on DC vaccine (Steinman and Pope, 2002;von Euw et al, 2008). In exploring a tumor vaccine, researchers have used a variety of strategies to develop a DC vaccine that can stimulate a tumor-specific immune response.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced apoptotic tumor cells on tumor cell antigens in mouse bladder cancer

Xie¹,

Ding²,

Hou³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Herein, the preparation of a dendritic cell (DC) vaccine with radiation-induced apoptotic tumor cells and its immunological effects on bladder cancer in C57BL/6 mice was investigated. We used radiation to obtain a MB49 cell antigen that was sensitive to bone marrow-derived DCs to prepare a DC vaccine. An animal model of tumor-bearing mice was established with the MB49 mouse bladder cancer cell line. Animals were randomly allocated to an experimental group or control group. DC vaccine or phosphate-buffered saline was given 7 days before inoculation with tumor cells. Each group consisted of 2 subgroups in which tumor volume and the survival of tumor-bearing mice were recorded. Tumor volumes and average tumor masses of mice administered DC vaccine loaded with radiation-induced apoptotic cells were significantly lower than those in the control group (P < 0.01). 7549Effects of DC vaccine with radiation-induced apoptotic cells ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 7548-7555 (2015) Survival in the experimental group was also longer than that in the control group, and 2 mice survived without tumor formation. In the DC vaccine group, 2 mice were alive without tumor growth after 30 days, and no tumor was observed at 30 days after subcutaneous inoculation of MB49 cells. The DC vaccine loaded with radiation-induced apoptotic tumor cells had an anti-tumor effect and was associated with increased survival in a bladder cancer model in mice.

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A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression

Cited by 54 publications

References 52 publications

Vaccination with Antigen-Transfected, NKT Cell Ligand–Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells

Vaccination with Antigen-Transfected, NKT Cell Ligand–Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced apoptotic tumor cells on tumor cell antigens in mouse bladder cancer

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