Abstract
hile being instrumental in the treatment of leukemic relapse after allogeneic hematopoietic stem cell transplantation, the impact of donor lymphocyte infusion (DLI) and its effectiveness remain debatable. Consequently it is widely accepted that more efforts are needed in order to make DLI more effective. This communication thus deals with the generation of specific CTLs in the clinical setting of HLA matched hematopoietic stem cell transplantation, to be used as an improved DLI treatment for post-transplantation relapsed leukemias. We assessed the potential of fused dendritic cells from donor origin, with leukemic cells from the HLA matched recipient for the generation of donor anti-tumor CTLs. Leukemic cells and donor dendritic cells were fused using polyethylene glycol (PEG). The hybrids were analyzed for double phenotype of both DC and tumor, and used for the education and generation of cytotoxic donor lymphocytes. Results demonstrate that efficient and specific CTLs can be generated and used in vitro for the elimination of the recipient tumor cells. These results form the basis for the establishment of a novel methodology aimed at generating active or passive anti-leukemic vaccine in relapsed patients.
Highlights
Cancer immunotherapy is hampered by the fact that tumor specific antigens are either unknown, non-immunogenic or that the tumor develops means to evade the host immune response [1,2,3]
The introduction of tumor specific antigens into dendritic cells leading to the generation of cytotoxic T Lymphocytes (CTLs) against malignant cells has already been proven to be effective [4,12]
Phenotype analysis 2 × 105 cells were used for phenotypic analysis using fluorescein isothiocyanate (FITC)-conjugated monoclonal antibodies against CD86, major histocompatibility complex (MHC) class I, II, and phycoerythrin (PE)-conjugated mAbs against CD14 (DAKO, Glostrup Denmark) and CD83 (Becton Dickinson, San Jose, CA, USA)
Summary
Cancer immunotherapy is hampered by the fact that tumor specific antigens are either unknown, non-immunogenic or that the tumor develops means to evade the host immune response [1,2,3]. DCs can be pulsed with liposomal DNA, tumor cells or apoptotic cell fragments, peptides eluted from tumor cells, membranes, lysates, RNA and more [13,14,15,16,17,18] Such strategies have generated positive in vitro immune responses directed against the relevant tumor cells. Cancer immunotherapy by DC/ tumor cell fusion hybrids using solid carcinoma cells, in mouse models or in vitro with human cells such as breast and ovarian carcinoma, has been shown to elicit potent anti tumor effects via the induction of immune responses against multiple tumor-associated antigens [14,19,20,21]
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