title: The expanding horizon of immunotherapy in the treatment of malignant disorders: allogeneic hematopoietic stem cell transplantation and beyond.
abstract: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a very effective therapeutic modality with curative potential in patients with hematological malignancies. The therapeutic efficacy is mainly based on the alloreactive reaction of donor lymphocytes against malignant cells of the recipient named as 'graft-versus-leukemia' or 'graft-versus-tumor' (GVL, GVT) effect. However, besides the beneficial GVL effect, alloreactive reaction attacks normal cells and provokes the deleterious 'graft-versus-host disease' (GVHD) which represents the major limitation of allo-SCT. Current trials have focused on a dual goal: augmentation of GVL and complete abolishment of GVHD. From a theoretical point of view complete dissociation of GVL from GVHD can occur by selecting antigenic targets present on malignant and absent from normal cells. Hematopoietic tissue-restricted minor histocompatibility antigens and leukemia or tumor-associated antigens are ideal candidates for tumor-targeted immunotherapy. Other options for inducing anti-tumor immunity in the absence of GVHD are natural killer (NK) cell immunotherapy, amplification of immune responses by using monoclonal antibodies, and bispecific T and NK-cell engagers. Genetically modified immune effectors such as T-cells armed with chimeric antigen receptors (CAR) or transduced with T-cell receptors with anti-tumor specificity are another exciting field of immunotherapy against malignancies.
authors.affiliation: Second Department of Internal Medicine, Propaedeutic, Attikon General University Hospital, University of Athens , Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsirigotis
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000276:immunology; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D007694:Killer Cells, Natural / Q000502:physiology; D007938:Leukemia / Q000628:therapy; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D015778:Minor Histocompatibility Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Cellular adoptive immunotherapy; graft versus host disease; graft versus leukemia effect; targeted therapy