Treatment with tumor-reactive Fab-IL-2 and Fab-staphylococcal enterotoxin A fusion proteins leads to sustained T cell activation, and long-term survival of mice with established tumors

• Published in: International journal of oncology Vol. 15; no. 5; p. 873
• Main Authors: Søgaard, M, Ohlsson, L, Kristensson, K, Rosendahl, A, Sjoberg, A, Forsberg, G, Kalland, T, Dohlsten, M
• Format: Journal Article
• Language: English
• Published: Greece 01-11-1999
• Subjects: Amino Acid Sequence; Animals; Antigens, Differentiation, T-Lymphocyte - analysis; Escherichia coli; Female; Humans; Immunoglobulin Fab Fragments - therapeutic use; Interleukin-2 - therapeutic use; Lung - immunology; Lung - pathology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - therapeutic use; Spleen - immunology; Spleen - pathology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Transfection; Tumor Cells, Cultured
• ISSN: 1019-6439
• DOI: 10.3892/ijo.15.5.873

C215Fab-IL-2 fusion protein, with full IL-2 and antigen binding activity, was produced in E. coli at high level (>50 mg/l). When co-administered with Fab-superantigen fusion protein (C215Fab-SEA) in mice strong and sustained T cell activation was observed. Combination treatment of mice carrying B16 melanoma transfected with C215 antigen was also more efficient than using C215Fab-SEA (p<0.01) or C215Fab-IL-2 alone (p<0.001). In a long-term survival experiment 5/12 mice having received combination treatment 5 days after i.v. inoculation of B16 cells survived >85 days. Improved therapeutic efficacy correlated with increased tumor infiltration by activated CD25+ T cells, indicating a T cell mediated mechanism.