NK cells from an AML patient have recovered in remission and reached comparable cytolytic activity to that of a healthy monozygotic twin mediated by the single-chain triplebody SPM-2
| Autor: | Todd A. Braciak, Claudia C. Roskopf, Sarah Wildenhain, Georg H. Fey, Uwe Jacob, Fuat Oduncu, Ingo Schubert, Karl-Peter Hopfner |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Cytotoxicity Immunologic Single chain triplebody (triplebodies) Antibody-dependent cellular cytotoxicity (ADCC) Myeloid medicine.medical_treatment CD33 Monozygotic twin Cancer immunotherapy General Biochemistry Genetics and Molecular Biology Young Adult Antigen Medizinische Fakultät hemic and lymphatic diseases Acute myeloid leukemia (AML) Humans Medicine ddc:610 Medicine(all) Biochemistry Genetics and Molecular Biology(all) business.industry Research Remission Induction Antibody-Dependent Cell Cytotoxicity Twins Monozygotic General Medicine Flow Cytometry medicine.disease Killer Cells Natural Leukemia Myeloid Acute Cytolysis Leukemia medicine.anatomical_structure Immunology Female Interleukin-3 receptor business Natural killer (NK) cells |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| DOI: | 10.1186/1479-5876-11-289 |
| Popis: | Background The capacity of patient’s Natural Killer cells (NKs) to be activated for cytolysis is an important prerequisite for the success of antibody-derived agents such as single-chain triplebodies (triplebodies) in cancer therapy. NKs recovered from AML patients at diagnosis are often found to be reduced in peripheral blood titers and cytolytic activity. Here, we had the unique opportunity to compare blood titers and cytolytic function of NKs from an AML patient with those of a healthy monozygotic twin. The sibling’s NKs were compared with the patient’s drawn either at diagnosis or in remission after chemotherapy. The cytolytic activities of NKs from these different sources for the patient’s autologous AML blasts and other leukemic target cells in conjunction with triplebody SPM-2, targeting the surface antigens CD33 and CD123 on the AML cells, were compared. Methods Patient NKs drawn at diagnosis were compared to NKs drawn in remission after chemotherapy and a sibling’s NKs, all prepared from PBMCs by immunomagnetic beads (MACS). Redirected lysis (RDL) assays using SPM-2 and antibody-dependent cellular cytotoxicity (ADCC) assays using the therapeutic antibody RituximabTM were performed with the enriched NKs. In addition, MACS-sorted NKs were analyzed for NK cell activating receptors (NCRs) by flow cytometry, and the release of TNF-alpha and IFN-gamma from blood samples of both siblings after the addition of the triplebody were measured in ELISA-assays. Results Patient NKs isolated from peripheral blood drawn in remission produced comparable lysis as NKs from the healthy twin against the patient’s autologous bone marrow (BM) blasts, mediated by SPM-2. The NCR receptor expression profiles on NKs from patient and twin were similar, but NK cell titers in peripheral blood were lower for samples drawn at diagnosis than in remission. Conclusions Peripheral blood NK titers and ex vivo cytolytic activities mediated by triplebody SPM-2 were comparable for cells drawn from an AML patient in remission and a healthy twin. If these results can be generalized, then NKs from AML patients in remission are sufficient in numbers and cytolytic activity to make triplebodies promising new agents for the treatment of AML. |
| Databáze: | OpenAIRE |
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