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

• Published in: Clinical cancer research Vol. 12; no. 24; pp. 7380 - 7388
• Main Authors: LESIMPLE, Thierry, NEIDHARD, Eve-Marie, BIREBENT, Brigitte, PHILIP, Irène, TOUJAS, Louis, CHOKRI, Mohamed, QUILLIEN, Véronique, VIGNARD, Virginie, LEFEUVRE, Claudia, ADAMSKI, Henri, LABARRIERE, Nathalie, CARSIN, André, MONNIER, Delphine, COLLET, Brigitte, CLAPISSON, Gilles
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.2006
• Subjects: Adult; Aged; Aged, 80 and over; Antibody Formation; Antigens, Neoplasm - chemistry; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Cancer; Cancer Vaccines - adverse effects; Cancer Vaccines - analysis; Cancer Vaccines - therapeutic use; clinical trial; dendritic cells; Dendritic Cells - chemistry; Dendritic Cells - transplantation; Dermatology; Disease-Free Survival; Female; Humans; Immunity, Cellular; Immunology; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Injections, Intralymphatic - methods; intralymphatic injection; intranodal injection; Life Sciences; Lymphatic Metastasis - immunology; Lymphatic Metastasis - pathology; Male; MART-1 Antigen; Medical sciences; melanoma; Melanoma - immunology; Melanoma - mortality; Melanoma - therapy; Middle Aged; Neoplasm Proteins - chemistry; Neoplasm Proteins - immunology; Peptides - chemistry; Peptides - immunology; Pharmacology. Drug treatments; Skin Neoplasms - immunology; Skin Neoplasms - mortality; Skin Neoplasms - therapy; Survival Analysis; Treatment Outcome; Tumors of the skin and soft tissue. Premalignant lesions; Human; Pulsed dendritic cell; Peptides; Malignant melanoma; Advanced stage; Malignant tumor; Metastasis
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-1879

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-1 and/or NA17-A peptides and keyhole limpet hemocyanin. The cells were matured overnight with Ribomunyl, a toll-like receptor ligand, and IFN-γ, 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. Results: Dendritic cell vaccination induced delayed-type hypersensitivity reactivity toward NA17-A-pulsed, keyhole limpet hemocyanin–pulsed, and Melan-A-pulsed dendritic cells in 6 of 10, 4 of 11, and 3 of 9 patients, respectively. Four of the 12 patients analyzed by tetramer staining showed a significantly increased frequency of Melan-A-specific T cells, including one patient vaccinated only with NA17-A-pulsed dendritic cells. Furthermore, 2 of the 12 analyzed patients had a significant increase of NA17-A-specific T cells, including one immunized after an optional additional treatment course. No objective clinical response was observed. Two patients were stabilized at 4 and 10 months and three patients are still alive at 30, 39, and 48 months. Conclusions: Injections into the lymphatic system of mature peptide-loaded dendritic cells with potential TH1 polarization capacities did not result in marked clinical results, despite immunologic responses in some patients. This highlights the need to improve our understanding of dendritic cell physiology.