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

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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.

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Acknowledgements

We are grateful to Annette Gaudin, Anne Trichet and Sandrine Abgrall for their skilled technical assistance. This work was supported by the Comités départementaux d'Ille-et-Vilaine et du Morbihan de la Ligue nationale contre le Cancer.

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Authors and Affiliations

  1. Centre Régional de Lutte Contre le Cancer Eugène Marquis, rue de la Bataille Flandres-Dunkerque, CD 44229, 35042 Rennes cedex, Rennes, France

    Thierry Lesimple, Annick Moisan, André Carsin, Bernard Meunier, Brigitte Collet, Véronique Quillien, Claudia Lefeuvre-Plesse & Louis Toujas

  2. Service de Dermatologie, Centre Hospitalier Régional, Rennes, France

    Isabelle Ollivier & Jacqueline Chevrant-Breton

  3. Service d'Oncologie médicale, Centre Hospitalier Régional, Grenoble, France

    Mireille Mousseau

  4. Etablissement de Transfusion Sanguine, Rennes, France

    Claudine Leberre

  5. Laboratoire d'immuno-hématologie, Centre Hospitalier Régional, Rennes, France

    Bernard Drenou

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  1. Thierry Lesimple
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  2. Annick Moisan
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  3. André Carsin
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  13. Louis Toujas
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Correspondence to Thierry Lesimple.

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Lesimple, T., Moisan, A., Carsin, A. et al. Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects. Cancer Immunol Immunother 52, 438–444 (2003). https://doi.org/10.1007/s00262-003-0390-y

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  • DOI: https://doi.org/10.1007/s00262-003-0390-y

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