DNA immunization against tissue-restricted antigens enhances tumor immunity after allogeneic hemopoietic stem cell transplantation
| Autor: | Miguel-Angel Perales, Vanessa M. Hubbard, Adi Diab, Alan N. Houghton, Adam A. Kochman, Manuel E. Engelhorn, Fariborz Mortazavi, Jedd D. Wolchok, Onder Alpdogan, Marcel R.M. van den Brink, Jeffrey M. Eng, Theis H. Terwey, Adam D. Cohen, Deonka Huggins, José A. Guevara-Patiño, Glenn Heller |
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| Rok vydání: | 2006 |
| Předmět: |
Graft Rejection
medicine.medical_treatment T-Lymphocytes Immunology Melanoma Experimental Graft vs Host Disease chemical and pharmacologic phenomena Hematopoietic stem cell transplantation Biology Epitope DNA vaccination Mice Antigen immune system diseases Antigens Neoplasm Cell Line Tumor medicine Vaccines DNA Immunology and Allergy Animals Transplantation Homologous Bone Marrow Transplantation Melanoma Hematopoietic Stem Cell Transplantation medicine.disease Transplantation Mice Inbred C57BL Leukocyte Transfusion surgical procedures operative Immunization Organ Specificity Female CD8 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 177(6) |
| ISSN: | 0022-1767 |
| Popis: | Malignant relapse remains a major problem for recipients of allogeneic hemopoietic stem cell transplantation (HSCT). We hypothesized that immunization of allogeneic HSCT recipients against tissue-restricted Ags using DNA vaccines would decrease the risk of relapse without enhancing graft-vs-host disease (GVHD). Using the mouse B16 melanoma model, we found that post-HSCT DNA immunization against a single tumor Ag induces tumor rejection that is significantly greater than HSCT alone in a T cell-depleted MHC-matched minor Ag-mismatched allogeneic HSCT model (LP → B6). In treatment models, post-HSCT DNA immunization provides significantly greater overall survival than the vaccine alone. Donor leukocyte infusion further enhances tumor-free survival, including in treatment models. There was no GVHD in HSCT recipients treated with DNA vaccination and donor leukocyte infusion. Further analysis demonstrated that these effects are dependent on CD8+ T cells of donor origin that recognize multiple epitopes. These results demonstrate that DNA immunization against tissue-restricted Ags after allogeneic T cell-depleted HSCT can induce potent antitumor effects without causing GVHD. |
| Databáze: | OpenAIRE |
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