Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering
| Autor: | Prakash Satwani, C. Wade-Harris, Joanne Kurtzberg, Weiwei Fortino, Diana Pickering, Lynn L. Simpson, Laxmi V. Baxi, Carmella van de Ven, Janet Ayello, Mitchell S. Cairo, Warren G. Sanger |
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| Rok vydání: | 2006 |
| Předmět: |
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Natural killer receptor Natural killer Cell Survival Lymphocyte T-Lymphocytes Transplantation Heterologous chemical and pharmacologic phenomena Mice SCID Mice Immunophenotyping Mice Inbred NOD Cytotoxic T cell Medicine Animals Humans Killer Cells Lymphokine-Activated Cryopreservation Transplantation Tissue Engineering business.industry Lymphokine-activated killer Lymphokine Infant Newborn Cord blood hemic and immune systems Hematology Fetal Blood Ex vivo Killer Cells Natural medicine.anatomical_structure Immunology business K562 Cells CD8 Cell Division |
| Zdroj: | Biology of Blood and Marrow Transplantation. 12(6):608-622 |
| ISSN: | 1083-8791 |
| DOI: | 10.1016/j.bbmt.2006.01.009 |
| Popis: | Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free medium with anti-CD3 and interleukins 2, 7, and 12 combined with antibody/cytokines for 48 hours. Immunophenotyping, cytotoxicity, and proliferation were evaluated. A significant expansion of CD3+ was seen, in addition to increases in lymphocyte subsets of CD8+, CD8+/CD25+, and CD3+/45RO+ versus medium alone. A significant enhancement of CD3 proliferation (P < .001), NK cytotoxicity, NK subset expansion, LAK cytotoxicity, and T-helper 1 subset expansion was also demonstrated. Significant enrichment was seen in NK CD16+/CD56+bright, CD16+/CD56+dim, CD56+bright and CD56+dim/KIR3DL1+, CD56+bright and CD56+dim/KIR2DL1+, CD56+bright and CD56+dim/KIR2DL2+ and CD94+/NKG2a+ subsets. These increases in CB NK subsets were in part secondary to augmentation of cell survival. Further, survival of NOD-SCID mice xenografted with human K562 cells and treated with CB cells expanded with antibody/cytokines was significantly higher than that in animals that received no treatment (phosphate buffered saline) and those that were treated with CB ex vivo expanded in medium alone (P < .005, respectively). These data suggest that cryopreserved CB cells could be ex vivo engineered for potential use as adoptive cancer cellular immunotherapy for donor lymphocyte infusion after CBT. |
| Databáze: | OpenAIRE |
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