Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization
| Autor: | Radha Ramesh, Barbara S. Slusher, Gregory D. Wands, Min Yang, Thomas M. Luby, Mary Lynne Hedley, Christine M. Barbon |
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| Rok vydání: | 2010 |
| Předmět: |
Cyclophosphamide
Regulatory T cell Drug Compounding T cell Immunology Biology T-Lymphocytes Regulatory Epitope Cell Line Epitopes Mice Antigen Antigens Neoplasm T-Lymphocyte Subsets Vaccines DNA medicine Animals Humans Cytotoxic T cell Avidity Mice Inbred C3H T lymphocyte medicine.anatomical_structure Cytochrome P-450 CYP1B1 Cancer research Female Immunization Aryl Hydrocarbon Hydroxylases Immunosuppressive Agents Spleen medicine.drug |
| Zdroj: | Cellular Immunology. 262:150-161 |
| ISSN: | 0008-8749 |
| Popis: | Cyclophosphamide in combination with immunotherapeutic approaches preferentially impinges on Treg activity and allows for robust generation of T cell effectors. Reduced dosages of cyclophosphamide are necessary to restrict its cytotoxic effects to the negative regulatory cell populations while sparing effector lymphocytes. We investigated cyclophosphamide dosing in combination with ZYC300, a PLG-encapsulated plasmid DNA vaccine which encodes the cytochrome P450 family member, CYP1B1, a known human tumor-associated antigen. In mice, three consecutive, low doses of cyclophosphamide comprised a superior regimen in enhancing the magnitude, diversity of epitopes, and avidity to individual epitopes of specific T cell responses when compared to regimens that used either a single low or a single high dose. Consecutive low doses of cyclophosphamide predominantly targeted Tregs while sparing overall T lymphocyte counts. Thus, we report the synergistic activity of pharmacologic Treg depletion with cyclophosphamide on quantitatively and qualitatively increasing T cell responses to a known human tumor-associated antigen. |
| Databáze: | OpenAIRE |
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