Moreover, in vivo persistence can be achieved by the overexpression of antiapoptotic proteins such as Bcl-2 or Bcl-xL. cell therapy. Many studies were conducted to evaluate the benefits of this exciting and potent new treatment modality. This review summarizes the history of adoptive immunotherapy, adoptive immunotherapy using CARs, the CAR manufacturing process, preclinical and clinical GDC-0834 Racemate studies, and the effectiveness and drawbacks of this strategy. strong class=”kwd-title” Keywords: Chimeric antigen receptor T cell, Hematological malignancies Abstract ?mmn sistemin kanser hcrelerini kontrol ve elimine etme ?zelli?ine sahip oldu?u g?sterilmi?tir. ?mmn-kontroll eliminasyonda kanser a??lar? ve hematopoietik k?k hcre naklini i?eren selller terapiler bulunmaktad?r. Adoptif T hcre transferi daha potent ve spesifiktir, hedef d??? toksisitesi azd?r. Klinik ?al??malarda iki tr T hcresi test edilmektedir: T hcre resept?r ve kimerik antijen resept?r (KAR) modifiye T hcreleri. 1 Temmuz 2014te Amerikan G?da ve ?la? Dairesi anti-CD19 ?AR modifiye GDC-0834 Racemate T hcre tedavisini ????r a?an tedaviler s?n?f?na alm??t?r. Bu yeni tedavi y?ntemini ve etkilerini ara?t?ran bir?ok ?al??ma yap?lm??t?r. Bu derleme adoptif immnoterapinin ge?mi?ini, ?AR modifiye T hcrelerini, retim srecini, klinik ve preklinik ?al??malar? ?zetlemektedir. INTRODUCTION Poor salvage chemotherapy success rates for refractory hematological diseases have necessitated novel approaches. Adoptive T-cell transfer has gained significant interest and clinical usage in hematology because of the off target GDC-0834 Racemate effects of allogeneic stem cell transplantation and life threatening graft versus host disease (GVHD). Therefore, research efforts have sought to generate more specific T cells with higher toxicity to tumors and not healthy targets. To achieve curative potential, T cell immunotherapy combines potency, specificity and persistence . Early approaches to adoptive T cell immunotherapy were based on the graft-versus-leukemia (GVL) effect mediated by donor lymphocyte infusion (DLI) hematopoietic stem cell transplantation (HSCT) and the therapeutic infusion of ex vivo expanded tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion for the treatment of advanced melanoma. However, DLI is usually associated with life-threatening forms of GVHD, and TILs require time-consuming procedures with unsuccessful results [2,3]. To overcome these drawbacks, genetically modified effector T cells have been developed as an alternative approach. In hematological malignancies, engineered T cell receptors (TCRs) and chimeric antigen receptors (CARs) are new powerful T-cell based immune therapies that target specific antigens. Reln CAR T cells have been used successfully in the treatment of solid and hematological malignancies recently. In the following sections, the history of adoptive immunotherapy, TCR gene therapy, CART cell production, and preclinical and clinical studies will be discussed. THE ROLE OF T CELLS IN CANCER AND T CELLL RECEPTOR GENE THERAPY In 1909, Paul Ehrlich first proposed that the immune defense system identifies and eliminates tumor cells . However, recent studies revealed that the immune response may be ineffective against tumor development due to immunological tolerance and anergy . Cancer immunoediting consists of three stages: elimination, equilibrium and escape. In the elimination stage, cancer is eliminated by intact innate and adaptive immunity, whereas in the equilibrium stage, variant tumor cells that develop genetic instability survive despite the immune attacks. Uncontrolled proliferation of variant tumor cells occurs in the escape stage . In 1890, William B Coley observed that patients with malignancies respond to the intratumoral inoculation of live bacterial organisms or bacterial toxins that cause tumors to express unique proteins that could trigger an immune response . Since the beginning of the 20th century, research has shown that most cancer cells carry overexpressed tumor-associated or tumor-specific antigens that are not present on healthy cells; this feature has led to the successful application of adoptive T-cell transfer. The discovery of T-cell growth factor, in vitro T-cell culture and the role of lymphodepletion have led to T-cell based therapy studies . The first successful study on T-cell transfer immunotherapy using autologous TILs was performed in advanced melanoma in 1990 . Since tumor infiltrating lymphocyte isolation was first attempted, in vitro expansion and re-infusion have been shown to be time-consuming and produce transient anti-tumor effects, and genetic engineering methods have been applied to create specific T cell-generated TCRs. The TCR is a heterodimer that carries information for defined tumor antigens GDC-0834 Racemate and is formed.