Tumor specific phage particles promote tumor regression in a mouse melanoma model.
Within cancer research, phage display libraries have been widely used for the identification of tumor targeting peptides and antibodies. Additionally, phages are known to be highly immunogenic; therefore we evaluated the immunotherapeutic potential of tumor specific phages to treat established solid tumors in a mouse model of melanoma. We developed two tumor specific phages, one derived from a peptide phage display library and one Fab expressing phage with known specificity, for the treatment of mice bearing palpable B16-F10 or B16/A2K(b) tumors. Therapy in B16-F10 tumor bearing mice with tumor specific phages was superior to treatment with non-tumor specific phages and lead to delayed tumor growth and increased survival. In B16/A2K(b )tumor bearing mice, therapy with tumor specific phages resulted in complete tumor regression and long-term survival in 50% of the mice. Histological analysis of tumors undergoing treatment with tumor specific phages revealed that phage administration induced a massive infiltration of polymorphonuclear neutrophils. Furthermore, phages induced secretion of IL-12 (p70) and IFN-gamma as measured in mouse splenocyte culture supernatants. These results demonstrate a novel, immunotherapeutic cancer treatment showing that tumor specific phages can promote regression of established tumors by recruitment of inflammatory cells and induction of Th1 cytokines.
Eriksson
Fredrik
F
Department of Oncology and Pathology, Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska Institute, Stockholm, Sweden. fredrik.eriksson@ki.se
Culp
W David
WD
Massey
Robert
R
Egevad
Lars
L
Garland
Donita
D
Persson
Mats A A
MA
Pisa
Pavel
P
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015723:Gene Library; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D007140:Immunoglobulin Fab Fragments