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
| Autor: | Atima Sharma, Nejat K. Egilmez, Edith Mathiowitz, Raji E. Nair, Yong S. Jong, Stacy A. Jones |
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| Rok vydání: | 2006 |
| Předmět: |
Genetically modified mouse
Cancer Research Receptor ErbB-2 T-Lymphocytes medicine.medical_treatment T cell Immunology Enzyme-Linked Immunosorbent Assay Mice Transgenic Biology Interferon-gamma Mice medicine Animals Immunology and Allergy Cytotoxic T cell Pharmacology Effector Granulocyte-Macrophage Colony-Stimulating Factor Mammary Neoplasms Experimental Immunotherapy Adoptive Transfer Immunohistochemistry Interleukin-12 Microspheres Cytokine medicine.anatomical_structure Interleukin 12 Female CD8 |
| Zdroj: | Journal of Immunotherapy. 29:10-20 |
| ISSN: | 1524-9557 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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