Specific peptide-mediated immunity against established melanoma tumors with dendritic cells requires IL-2 and fetal calf serum-free cell culture.

Abstract

Melanoma, despite its aggressive growth characteristics, is an antigenic tumor expressing several characterized neo- and differentiation antigens. Dendritic cells (DC) when pulsed with defined peptides have been shown to effectively induce melanoma-specific T cell responses in humans and mice. These protect animals from challenge with melanoma, but so far have failed to induce significant tumor regressions. To study the efficacy of DC-based anti-tumor vaccinations, we set up a therapeutic model using C57BL/6J mice with established pulmonary and subcutaneous metastases induced by the B16-melanoma cell line B78-D14. Mice were vaccinated twice with 20,000 antigen-presenting cells, either bone marrow-derived DC or epidermal Langerhans cells (LC), which were loaded with the tyrosinase-related protein 2 (TRP2) peptide. Generally, DC cultured with fetal calf serum (FCS) induced a dominant unspecific response. This was not seen using LC cultured without serum; however, vaccination with TRP2-loaded FCS-free LC alone failed to influence the growth of established B16 tumors. A reproducible reduction of tumor size and weight was only obtained if LC vaccinations with TRP2 were followed by a 5-day treatment of mice with 200,000 IU IL-2 intraperitoneally twice/daily. Omitting the TRP2 peptide abolished the efficacy of this combined treatment, demonstrating the crucial role of priming a melanoma-specific T cell response. Microcytotoxic assays performed with spleen-derived T cells and melanoma as well as congenic fibroblast lines as targets confirmed the TRP2-dependent specificity of LC-induced immune responses. Thus, despite the fact that tumor-specific T cells were primed, an additional IL-2-dependent stimulus was needed to translate this immune response into a therapeutic effect against established tumors.

• Authors: Andreas O Eggert, Jürgen C Becker, Michael Ammon, Alexander D McLellan, German Renner, Angela Merkel, Eva-B Bröcker, Eckhart Kämpgen
• Journal: European journal of immunology (Eur J Immunol) Vol. 32 Issue 1 Pg. 122-7 (01 2002) ISSN: 0014-2980 [Print] Germany
• PMID: 11754352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Culture Media, Serum-Free
• Interleukin-2
• Peptides
• Serum Albumin, Bovine
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Animals
• Antigens, Neoplasm (immunology, therapeutic use)
• Bone Marrow Cells (immunology)
• Culture Media, Serum-Free
• Dendritic Cells (cytology, immunology)
• Immunotherapy
• Interleukin-2 (administration & dosage, immunology)
• Intramolecular Oxidoreductases (immunology, therapeutic use)
• Melanoma, Experimental (prevention & control)
• Mice
• Mice, Inbred C57BL
• Neoplasm Metastasis
• Peptides (immunology, therapeutic use)
• Serum Albumin, Bovine
• Tumor Cells, Cultured