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American Journal of Blood Research (1)
International Journal of Molecular Sciences (1)
Spyridonidis, Alexandros (3)
Themeli, Maria (2)
Finke, Juergen (1)
Liga, Maria (1)
Waterhouse, Miguel (1)
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A long road of T-cells to cure cancer: from adoptive immunotherapy with unspecific cellular products to donor lymphocyte infusions and transfer of engineered tumor-specific T-cells
American Journal of Blood Research
The notion that immunocompetent cells, contained within adult bone marrow or peripheral blood, are capable of mediating an antitumor effect was first validated experimentally in 1957. T-cell immunotherapy for malignant disease is now routinely used in the context of allogeneic bone marrow transplantation. After 50 years of investigations into the use of T-cells for cancer therapy, adoptive cellular immunotherapy for cancer has progressed from the delivery of unspecific cellular products to the transfer of engineered tumor-specific T-cells. Adoptive cellular immunotherapy for cancer has now reached a stage of increasing feasibility and efficacy.
Immunocompetent cells; antitumor effect; T-cell immunotherapy; allogeneic bone marrow transplantation; tumor-specific T-cells
DNA chimerism and its consequences after allogeneic hematopoietic cell transplantation
The unphysiological formation of biological chimeras after allogeneic hematopoietic cell transplantation is not free of consequences. Recent findings suggest that in the transplant recipient some epithelial cells reveal, unexpectedly, donor-derived genotype and/or acquire genomic alterations. Since both phenomena are presented in the host epithelium, one could argue that they might be etiologically linked through a common background mechanism. We recently proposed that the incessant charge of the transplant recipient with donor-DNA and its integration in host epithelium by horizontal DNA transference may indeed be operative in the generation of epithelial cells with donor derived genome. On the other hand, the incessant incorporation of the foreign DNA into the host genome may result in genomic alterations. Lymphocyte-epithelial interactions between the two genetically distinct cell populations in the transplant recipient should be investigated more precisely not only in cellular but also in molecular level.
hematopoietic cell transplantation; chimerism; horizontal gene transfer; genomic instability; secondary cancer
DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation
International Journal of Molecular Sciences
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in humans, following hematoablative treatment, results in biological chimeras. In this case, the transplanted hematopoietic, immune cells and their derivatives can be considered the donor genotype, while the other tissues are the recipient genotype. The first sequel, which has been recognized in the development of chimerical organisms after allo-HSCT, is the graft versus host (GvH) reaction, in which the new developed immune cells from the graft recognize the host’s epithelial cells as foreign and mount an inflammatory response to kill them. There is now accumulating evidence that this chronic inflammatory tissue stress may contribute to clinical consequences in the transplant recipient. It has been recently reported that host epithelial tissue acquire genomic alterations and display a mutator phenotype that may be linked to the occurrence of a GvH reaction. The current review discusses existing data on this recently discovered phenomenon and focuses on the possible pathogenesis, clinical significance and therapeutic implications.
bone marrow transplantation; mismatch repair; microsatellite instability; graft-versus-host reaction
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