Biodistribution of radiolabelled human dendritic cells injected by various routes

Quillien, Véronique; Moisan, Annick; Carsin, A; Lesimple, Thierry; Lefeuvre, Claudia; Adamski, H.; Bertho, Nicolas; Devillers, Anne; Leberre, C.; Toujas, Louis

doi:10.1007/s00259-005-1825-9

Cited by 61 publications

(37 citation statements)

References 26 publications

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“…Indeed, intralymphatic injection enabled the dendritic cells to reach 8 to 10 inguinal, crural, and iliac nodes, as reported previously (12). Intranodal injected dendritic cells probably reached the target lymph node in f50% of cases, if we refer to recent studies with magnetically labeled dendritic cells and magnetic resonance tracking (18).…”

Section: Discussionmentioning

confidence: 58%

“…The biological properties and the biodistribution of radiolabeled dendritic cells injected by intralymphatic, intranodal, and i.d. routes have been reported and discussed in a companion article (12).…”

Section: Discussionmentioning

confidence: 99%

“…This cytokine is known to play a critical role in driving CD4 + T cells to TH1 polarization, a property essential for the development of T-cell -mediated antitumor response. As a matter of fact, dendritic cells matured with Ribomunyl and IFN-g and cocultured with T cells are known to induce TH1-characteristic cytokines (12,16,17). Third, to minimize the risk of poor migration of dendritic cells toward lymph nodes, the first cell injection was done into a lymphatic vessel.…”

Section: Discussionmentioning

confidence: 99%

“…Translational research included the evaluation of immune response and the biodistribution of injected radiolabeled cells. This last point has been described elsewhere (12).…”

Section: Methodsmentioning

confidence: 99%

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Immunologic and Clinical Effects of Injecting Mature Peptide-Loaded Dendritic Cells by Intralymphatic and Intranodal Routes in Metastatic Melanoma Patients

Lesimple

Neidhard

Vignard

et al. 2006

Clinical Cancer Research

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Purpose: A phase I/II trial was conducted to evaluate clinical and immunologic responses after intralymphatic and intranodal injections of mature dendritic cells. Experimental Design: Fourteen patients with a metastatic melanoma received matured dendritic cells, loaded with Melan-A/MART-1and/or NA17-A peptides and keyhole limpet hemocyanin.The cells were matured overnight with Ribomunyl, a toll-like receptor ligand, and IFN-g, which ensured the production of high levels of interleukin-12p70. Dendritic cells were injected at monthly intervals, first into an afferent lymphatic and then twice intranodally. Immunologic responses were monitored by tetramer staining of circulating CD8 + lymphocytes and delayed-type hypersensitivity tests.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Translational research included the evaluation of immune response and the biodistribution of injected radiolabeled cells. This last point has been described elsewhere (12).…”

Section: Methodsmentioning

confidence: 99%

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Immunologic and Clinical Effects of Injecting Mature Peptide-Loaded Dendritic Cells by Intralymphatic and Intranodal Routes in Metastatic Melanoma Patients

Lesimple

Neidhard

Vignard

et al. 2006

Clinical Cancer Research

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“…(9 -16), i.n. (9,11,17), and intralymphatic (11,18) injection did DC migrate to the draining lymph node regions. More substantial evidence was obtained in our previous study, in which DC were labeled with both 111 In and paramagnetic iron oxide particles (SPIO), which is a suitable contrast agent for magnetic resonance imaging (17).…”

mentioning

confidence: 99%

Limited Amounts of Dendritic Cells Migrate into the T-Cell Area of Lymph Nodes but Have High Immune Activating Potential in Melanoma Patients

Verdijk¹,

Aarntzen²,

Lesterhuis³

et al. 2009

Clinical Cancer Research

176

184

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Purpose: The success of immunotherapy with dendritic cells (DC) to treat cancer is dependent on effective migration to the lymph nodes and subsequent activation of antigen-specificTcells. In this study, we investigated the fate of DC after intradermal (i.d.) or intranodal (i.n.) administration and the consequences for the immune activating potential of DC vaccines in melanoma patients. Experimental Design: DC were i.d. or i.n. administered to 25 patients with metastatic melanoma scheduled for regional lymph node resection. To track DC in vivo with scintigraphic imaging and in lymph nodes by immunohistochemistry, cells were labeled with both [ 111 In]-indium and superparamagnetic iron oxide. Results: After i.d. injection, maximally 4% of the DC reached the draining lymph nodes. When correctly delivered, all DC were delivered to one or more lymph nodes after i.n. injection. Independent of the route of administration, large numbers of DC remained at the injection site, lost viability, and were cleared by infiltrating CD163+ macrophages within 48 hours. Interestingly, 87 F 10% of the surviving DC preferentially migrated into the T-cell areas, where they induced antigen-specificT-cell responses. Even though more DC reached theT-cell areas, i.n. injection of DC induced similar antigen-specific immune responses as i.d. injection. Immune responses were already induced with <5 Â 10 5 DC migrating into theT-cell areas. Conclusions: Monocyte-derived DC have high immune activating potential irrespective of the route of vaccination. Limited numbers of DC in the draining lymph nodes are sufficient to induce antigen-specific immunologic responses.

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Oncolytic virotherapy enhances the efficacy of a cancer vaccine by modulating the tumor microenvironment

Koske

Rössler

Pipperger

et al. 2019

Intl Journal of Cancer

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The efficacy of cancer vaccines has been limited by the immunosuppressive tumor microenvironment, which can be alleviated by immune checkpoint inhibitor (ICI) therapy. Here, we tested if oncolytic viruses (OVs), similar to ICI, can also synergize with cancer vaccines by modulating the tumor microenvironment. VSV‐GP, a chimeric vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, is a promising new OV candidate. Here, we show that in mouse B16‐OVA melanoma, combination treatment of VSV‐GP with an ovalbumin (OVA) peptide‐loaded dendritic cell (DC) vaccine (DCVacc) significantly enhanced survival over the single agent therapies, although both DCVacc and DCVacc/VSV‐GP treatments induced comparable levels of OVA‐specific CD8 T cell responses. Virus replication was minimal so that direct viral oncolysis in B16‐OVA did not contribute to this synergism. The strong therapeutic effect of the DCVacc/VSV‐GP combination treatment was associated with high numbers of tumor‐infiltrating, highly activated T cells and the relative reduction of regulatory T cells in treated and contra‐lateral nontreated tumors. Accordingly, depletion of CD8 T cells but not natural killer cells abrogated the therapeutic effect of DCVacc/VSV‐GP supporting the crucial role of CD8 T cells. In addition, a drastic increase in several proinflammatory cytokines was observed in VSV‐GP‐treated tumors. Taken together, OVs, similar to ICI, have the potential to markedly increase the efficacy of cancer vaccines by alleviating local immune suppression in the tumor microenvironment.

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Biodistribution of radiolabelled human dendritic cells injected by various routes

Cited by 61 publications

References 26 publications

Immunologic and Clinical Effects of Injecting Mature Peptide-Loaded Dendritic Cells by Intralymphatic and Intranodal Routes in Metastatic Melanoma Patients

Immunologic and Clinical Effects of Injecting Mature Peptide-Loaded Dendritic Cells by Intralymphatic and Intranodal Routes in Metastatic Melanoma Patients

Limited Amounts of Dendritic Cells Migrate into the T-Cell Area of Lymph Nodes but Have High Immune Activating Potential in Melanoma Patients

Oncolytic virotherapy enhances the efficacy of a cancer vaccine by modulating the tumor microenvironment

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