Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy
| Autor: | Daniela Montagna, Rita Maccario, Enrica Montini, Peggy Farness, Antonia Moretta, Antonella Vitiello, Patrizia Comoli, Young Yang, Franco Locatelli, Vittorio Rosti |
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| Rok vydání: | 2001 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer medicine.medical_treatment Immunology Priming (immunology) CD8-Positive T-Lymphocytes Lymphocyte Activation Immunotherapy Adoptive Biochemistry Cell Line Cell therapy HLA Antigens medicine Humans Cytotoxic T cell CD40 Antigens Bone Marrow Transplantation business.industry Interleukin-7 Myeloid leukemia Dendritic Cells Cell Biology Hematology Immunotherapy medicine.disease Interleukin-12 Leukemia Myeloid Acute Leukemia medicine.anatomical_structure Histocompatibility Bone marrow business T-Lymphocytes Cytotoxic |
| Zdroj: | Blood. 98:3359-3366 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v98.12.3359 |
| Popis: | Adoptive cellular immunotherapy has proven to be a successful approach in preventing and curing cytomegalovirus infection and Epstein-Barr virus–associated lymphomas after bone marrow transplantation. Translation of this approach for preventing leukemia relapse after bone marrow transplantation might require ex vivo priming and long-term maintenance of leukemia blast-specific T cells. To accomplish this goal, procedures were optimized for the in vitro priming of naive CD8 using dendritic cells activated by CD40 ligation, interleukin-12 (IL-12), and IL-7. Using T lymphocytes and dendritic cells obtained from HLA-matched allogeneic bone marrow transplantation donors and leukemia blasts as a source of tumor antigens, anti–acute myeloid leukemia cytotoxic T lymphocytes (CTLs) were induced. In these experiments, it was found that though it is possible to induce CTLs using immature dendritic cells, IL-12, and IL-7, obtaining long-term CTLs requires the presence of CD4 T cells in the priming phase. Using this approach, long-term antileukemia CTL lines could be generated from 4 of 4 bone marrow donors. Because this procedure does not require definition of the target antigen and because it selects responding cells from a virgin T-cell repertoire, its general application is suggested in adoptive immunotherapy and in the definition of tumor rejection antigens. |
| Databáze: | OpenAIRE |
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