DNA immunization against tissue-restricted antigens enhances tumor immunity after allogeneic hemopoietic stem cell transplantation Journal Article
| Authors: | Perales, M. A.; Diab, A.; Cohen, A. D.; Huggins, D. W.; Guevara-Patiño, J. A.; Hubbard, V. M.; Engelhorn, M. E.; Kochman, A. A.; Eng, J. M.; Mortazavi, F.; Alpdogan, O.; Terwey, T. H.; Heller, G.; Wolchok, J. D.; Houghton, A. N.; van den Brink, M. R. M. |
| Article Title: | DNA immunization against tissue-restricted antigens enhances tumor immunity after allogeneic hemopoietic stem cell transplantation |
| Abstract: | 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. Copyright © 2006 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; transplantation, homologous; overall survival; nonhuman; cd8+ t lymphocyte; t lymphocyte; t-lymphocytes; mouse; animals; mice; melanoma; animal experiment; animal model; hematopoietic stem cell transplantation; cell line, tumor; tumor antigen; mice, inbred c57bl; antigens, neoplasm; antigen recognition; epitope; organ specificity; graft versus host reaction; melanoma, experimental; allogeneic hematopoietic stem cell transplantation; cancer relapse; tumor immunity; dna vaccine; graft rejection; bone marrow transplantation; graft vs host disease; tumor rejection; vaccines, dna; immunization; leukocyte transfusion |
| Journal Title: | Journal of Immunology |
| Volume: | 177 |
| Issue: | 6 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2006-09-15 |
| Start Page: | 4159 |
| End Page: | 4167 |
| Language: | English |
| PUBMED: | 16951381 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 4 June 2012" - "CODEN: JOIMA" - "Source: Scopus" |
