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Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects.

Identifieur interne : 003293 ( Main/Exploration ); précédent : 003292; suivant : 003294

Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects.

Auteurs : RBID : pubmed:12690521

English descriptors

Abstract

Patients' autologous macrophages (AM) were used as antigen-presenting cells (APC) in a vaccination protocol against malignant melanoma. AM were administered by various routes, including intralymphatic, since these cells did not express CCR7, a molecule required for APC migration to lymph nodes. Seven HLA-A2 patients with metastatic melanoma-two classified as M1 and five as M3-were included in the study. AM were produced from leukapheresis-separated mononuclear cells by 7-day culture with granulocyte-macrophage colony-stimulating factor. After separation by elutriation, AM were frozen in aliquots and subsequently thawed at monthly intervals, exposed to MAGE-3(271-279) peptide and injected subcutaneously into lymph nodes or into one peripheral lymph vessel. Intradermal tests were performed before and after treatment to determine peptide reactivity. No acute toxicity was observed following injection. One M1 patient had a 7-mm induration intradermal reaction response and was stabilized for 64 weeks. The M3 patients did not show any immunological or clinical response. In 11 patients, the biodistribution of 111In-labeled AM was investigated. There was no clear evidence that AM injected intradermally or subcutaneously left the site of injection. After injection into a lymph vessel of the foot region, scintigraphs showed five to ten popliteal and inguinocrural lymph nodes. This appeared to be the most efficient way to administer rapidly and safely large amounts of peptide-loaded APC into lymph nodes.

DOI: 10.1007/s00262-003-0390-y
PubMed: 12690521

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Le document en format XML

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<title xml:lang="en">Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects.</title>
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<country xml:lang="fr">France</country>
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<name sortKey="Moisan, Annick" uniqKey="Moisan A">Annick Moisan</name>
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<author>
<name sortKey="Carsin, Andre" uniqKey="Carsin A">André Carsin</name>
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<author>
<name sortKey="Ollivier, Isabelle" uniqKey="Ollivier I">Isabelle Ollivier</name>
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<name sortKey="Mousseau, Mireille" uniqKey="Mousseau M">Mireille Mousseau</name>
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<name sortKey="Meunier, Bernard" uniqKey="Meunier B">Bernard Meunier</name>
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<name sortKey="Leberre, Claudine" uniqKey="Leberre C">Claudine Leberre</name>
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<name sortKey="Collet, Brigitte" uniqKey="Collet B">Brigitte Collet</name>
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<name sortKey="Quillien, Veronique" uniqKey="Quillien V">Véronique Quillien</name>
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<name sortKey="Drenou, Bernard" uniqKey="Drenou B">Bernard Drenou</name>
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<name sortKey="Lefeuvre Plesse, Claudia" uniqKey="Lefeuvre Plesse C">Claudia Lefeuvre-Plesse</name>
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<name sortKey="Chevrant Breton, Jacqueline" uniqKey="Chevrant Breton J">Jacqueline Chevrant-Breton</name>
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<name sortKey="Toujas, Louis" uniqKey="Toujas L">Louis Toujas</name>
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<term>Antigens, Neoplasm (therapeutic use)</term>
<term>Female</term>
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<term>Macrophages (drug effects)</term>
<term>Macrophages (physiology)</term>
<term>Macrophages (radionuclide imaging)</term>
<term>Male</term>
<term>Melanoma (radionuclide imaging)</term>
<term>Melanoma (therapy)</term>
<term>Middle Aged</term>
<term>Neoplasm Proteins (therapeutic use)</term>
<term>Peptide Fragments</term>
<term>Receptors, CCR7</term>
<term>Receptors, Chemokine (metabolism)</term>
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<term>Indium Radioisotopes</term>
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<term>Antigens, CD</term>
<term>Granulocyte-Macrophage Colony-Stimulating Factor</term>
<term>HLA-A2 Antigen</term>
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<term>Macrophages</term>
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<term>Antigen-Presenting Cells</term>
<term>Lymph Nodes</term>
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<term>Macrophages</term>
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<term>Lymph Nodes</term>
<term>Macrophages</term>
<term>Melanoma</term>
<term>Skin Neoplasms</term>
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<div type="abstract" xml:lang="en">Patients' autologous macrophages (AM) were used as antigen-presenting cells (APC) in a vaccination protocol against malignant melanoma. AM were administered by various routes, including intralymphatic, since these cells did not express CCR7, a molecule required for APC migration to lymph nodes. Seven HLA-A2 patients with metastatic melanoma-two classified as M1 and five as M3-were included in the study. AM were produced from leukapheresis-separated mononuclear cells by 7-day culture with granulocyte-macrophage colony-stimulating factor. After separation by elutriation, AM were frozen in aliquots and subsequently thawed at monthly intervals, exposed to MAGE-3(271-279) peptide and injected subcutaneously into lymph nodes or into one peripheral lymph vessel. Intradermal tests were performed before and after treatment to determine peptide reactivity. No acute toxicity was observed following injection. One M1 patient had a 7-mm induration intradermal reaction response and was stabilized for 64 weeks. The M3 patients did not show any immunological or clinical response. In 11 patients, the biodistribution of 111In-labeled AM was investigated. There was no clear evidence that AM injected intradermally or subcutaneously left the site of injection. After injection into a lymph vessel of the foot region, scintigraphs showed five to ten popliteal and inguinocrural lymph nodes. This appeared to be the most efficient way to administer rapidly and safely large amounts of peptide-loaded APC into lymph nodes.</div>
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<AbstractText>Patients' autologous macrophages (AM) were used as antigen-presenting cells (APC) in a vaccination protocol against malignant melanoma. AM were administered by various routes, including intralymphatic, since these cells did not express CCR7, a molecule required for APC migration to lymph nodes. Seven HLA-A2 patients with metastatic melanoma-two classified as M1 and five as M3-were included in the study. AM were produced from leukapheresis-separated mononuclear cells by 7-day culture with granulocyte-macrophage colony-stimulating factor. After separation by elutriation, AM were frozen in aliquots and subsequently thawed at monthly intervals, exposed to MAGE-3(271-279) peptide and injected subcutaneously into lymph nodes or into one peripheral lymph vessel. Intradermal tests were performed before and after treatment to determine peptide reactivity. No acute toxicity was observed following injection. One M1 patient had a 7-mm induration intradermal reaction response and was stabilized for 64 weeks. The M3 patients did not show any immunological or clinical response. In 11 patients, the biodistribution of 111In-labeled AM was investigated. There was no clear evidence that AM injected intradermally or subcutaneously left the site of injection. After injection into a lymph vessel of the foot region, scintigraphs showed five to ten popliteal and inguinocrural lymph nodes. This appeared to be the most efficient way to administer rapidly and safely large amounts of peptide-loaded APC into lymph nodes.</AbstractText>
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