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.
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.
Søgaard
M
M
Active Biotech Research AB, S-220 07 Lund, Sweden.
Ohlsson
L
L
Kristensson
K
K
Rosendahl
A
A
Sjoberg
A
A
Forsberg
G
G
Kalland
T
T
Dohlsten
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins