Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects.
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.
Lesimple
Thierry
T
Centre Régional de Lutte Contre le Cancer Eugène Marquis, rue de la Bataille Flandres-Dunkerque, CD 44229, 35042 Rennes, France. lesimple@rennes.fnclcc.fr
Moisan
Annick
A
Carsin
André
A
Ollivier
Isabelle
I
Mousseau
Mireille
M
Meunier
Bernard
B
Leberre
Claudine
C
Collet
Brigitte
B
Quillien
Véronique
V
Drenou
Bernard
B
Lefeuvre-Plesse
Claudia
C
Chevrant-Breton
Jacqueline
J
Toujas
Louis
L
D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007205:Indium Radioisotopes; D007267:Injections / Q000379:methods; D007428:Intradermal Tests; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000276:immunology; D008264:Macrophages / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D010446:Peptide Fragments; D011877:Radionuclide Imaging; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C515370:CCR7 protein, human; D015789:HLA-A2 Antigen; D007205:Indium Radioisotopes; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor