IL-12 + GM-CSF microsphere therapy induces eradication of advanced spontaneous tumors in her-2/neu transgenic mice but fails to achieve long-term cure due to the inability to maintain effector T-cell activity.
A single intratumoral injection of interleukin-12 and granulocyte-macrophage colony-stimulating factor-encapsulated microspheres induced the regression of advanced spontaneous mammary tumors, suppressed additional tumor development, and enhanced survival in her-2/neu transgenic mice. Posttherapy tumor eradication was dependent on both CD4+ and CD8+ T cells and correlated with the tumor infiltration kinetics of a transient effector T-cell response. Upon long-term monitoring, tumor regression was found to be temporary, and disease-free survival was not achieved despite the development of systemic anti-tumor cytotoxic T-cell memory and antibody responses. Repeated immunization of mice enhanced short-term tumor suppression, resulting in the complete regression of primary tumors in up to 40% of the mice, but did not improve long-term survival owing to recurrence. The failure of chronic therapy to achieve complete cure was associated with an inability to maintain the intensity of the posttherapy effector T-cell response in this model.
Nair
Raji E
RE
James Graham Brown Cancer Center, Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
Jong
Yong S
YS
Jones
Stacy A
SA
Sharma
Atima
A
Mathiowitz
Edith
E
Egilmez
Nejat K
NK
D019264:Adoptive Transfer; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects; D018664:Interleukin-12 / Q000008:administration & dosage*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008863:Microspheres; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases