Abstract:
:Chimeric antigen receptor (CAR) T-cell therapy represents a major advancement in personalized cancer treatment. In this strategy, a patient's own T cells are genetically engineered to express a synthetic receptor that binds a tumor antigen. CAR T cells are then expanded for clinical use and infused back into the patient's body to attack and destroy chemotherapy-resistant cancer. Dramatic clinical responses and high rates of complete remission have been observed in the setting of CAR T-cell therapy of B-cell malignancies. This resulted in two recent FDA approvals of CAR T cells directed against the CD19 protein for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Thus, CAR T cells are arguably one of the first successful examples of synthetic biology and personalized cellular cancer therapy to become commercially available. In this review, we introduce the concept of using CAR T cells to break immunological tolerance to tumors, highlight several challenges in the field, discuss the utility of biomarkers in the context of predicting clinical responses, and offer prospects for developing next-generation CAR T cell-based approaches that will improve outcome.
journal_name
Am J Hematoljournal_title
American journal of hematologyauthors
Feins S,Kong W,Williams EF,Milone MC,Fraietta JAdoi
10.1002/ajh.25418subject
Has Abstractpub_date
2019-05-01 00:00:00pages
S3-S9issue
S1eissn
0361-8609issn
1096-8652journal_volume
94pub_type
杂志文章,评审abstract::Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on rena...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21072
更新日期:2008-03-01 00:00:00
abstract::Sickle cell disease (SCD) nephropathy and lower estimated glomerular filtration rate (eGFR) are risk factors for early mortality. Furthermore, rate of eGFR decline predicts progression to end-stage renal disease in many clinical settings. However, factors predicting renal function decline in SCD are poorly documented....
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.25263
更新日期:2018-12-01 00:00:00
abstract::Forty-one patients with polycythemia vera (PV) according to the PVSG criteria were analysed retrospectively from January 1960 to March 1996. There were 23 male and 18 female patients with a median follow-up of 66.5 months (3-431 months). Median age was 62 (range: 37-85). The median hemoglobin level at diagnosis was 18...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199709)56:1<59::aid-ajh12>
更新日期:1997-09-01 00:00:00
abstract::Polycythemia vera (PV) is a myeloproliferative disorder characterized by thrombotic and, less often, bleeding complications. Many mechanisms have been advanced to explain the occurrence of these complications, none of them satisfactory. We examined a cohort of 27 patients with PV, secondary erythrocytosis, and essenti...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199903)60:3<196::aid-ajh5>
更新日期:1999-03-01 00:00:00
abstract::A 25-year-old African-American man with sickle cell-beta(+)-thalassemia presented with acute asthma of 2 days' duration. The asthma was well controlled by 48 hr, and parenteral medications were changed to oral bronchodilators and steroids. Sixty hours after presentation, he developed pain similar to that of sickle cel...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830460418
更新日期:1994-08-01 00:00:00
abstract::Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib +...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.23358
更新日期:2013-02-01 00:00:00
abstract::A 71-year-old woman and her elder sister developed ligneous conjunctivitis after ocular surgery. Laboratory tests demonstrated that the proband and her sister had 6.6% and 8.1% of plasminogen activity, and 1.2 and 1.4 mg/dl of antigen, respectively. Thus, they were diagnosed as having severe type I plasminogen deficie...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21402
更新日期:2009-06-01 00:00:00
abstract::The improved microchromatographic procedure for the detection of Hb-S and/or Hb-C in cord blood at birth (Schroeder et al.: J. Lab Clin Med 86:528-532, 1975) as well as a modification thereof may also be used for the quantitative determination of Hb-F in the presence of Hb-S and/or Hb-C. However, Hb-A interferes and m...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830010308
更新日期:1976-01-01 00:00:00
abstract::A significant anemia develops in Buffalo rats bearing the Morris hepatoma 7777. By indiceal measurements the red blood cells (RBCs) appear to be microcytic and hypochromic. Ferrokinetic studies demonstrate a decreased uptake of iron in the bone marrow and an increased incorporation of iron in the spleens of the tumor-...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830070205
更新日期:1979-01-01 00:00:00
abstract::We report here a patient with de novo acute myelocytic leukemia with trilineage myelodysplasia (AML/TMDS) in whom cytogenetic analysis was normal at diagnosis and in whom Philadelphia chromosome (Ph1) with monosomy 7 emerged at the terminal stage of the disease. Reverse transcription polymerse chain reaction (RT-PCTR)...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830490413
更新日期:1995-08-01 00:00:00
abstract::Expression of alkaline phosphatase (ALP) on the surface membrane of neutrophils (mNAP) was studied by immunofluorescence using an anti-ALP monoclonal antibody. Fluorescent intensity distribution of mNAP was analyzed using FACS (fluorescence-activated cell sorter). The mean fluorescent intensity (MFI) of the mNAP in th...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199901)60:1<12::aid-ajh3>3
更新日期:1999-01-01 00:00:00
abstract::The trial CICL670AUS04 was a single-arm, open-label study of the cardiac efficacy of 18 months of deferasirox monotherapy [1]. Cardiac response in this study was related to the degree of liver siderosis. Patients with mild to moderate liver siderosis improved their cardiac T2* while more severely siderotic patients di...
journal_title:American journal of hematology
pub_type: 临床试验,信件
doi:10.1002/ajh.21830
更新日期:2010-10-01 00:00:00
abstract::Eighteen patients with acute nonlymphocytic leukemia (ANLL), aged 17-73 years, were treated with high-dose cytosine arabinoside (HD-Ara-C) using 3 g/m2 IV q 12 hours X 12 doses. Seven patients were treated for relapse and four (57%) obtained a complete remission with a median duration of 19.5 weeks. In nine patients, ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830160108
更新日期:1984-01-01 00:00:00
abstract::In this study we describe the time-dependent effects of a high dose (750 micrograms/ml/24 hr) continuous infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on monocyte number, cytokine release, and superoxide anion production. Blood was taken from patients prior to rhGM-CSF infus...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830430410
更新日期:1993-08-01 00:00:00
abstract:DISEASE OVERVIEW:Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,000 new patients annually and representing approximately 11% of all lymphomas in the United States. DIAGNOSIS:HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymph...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.23348
更新日期:2012-12-01 00:00:00
abstract::Patients presenting with Hodgkin's disease (HD) may show lung involvement characterized by contiguous spread from ipsilateral hilar lymph nodes. Lung consolidation or noncontiguous pulmonary involvement makes an alternative diagnosis more likely. This report describes a patient with HD in whom concurrent pulmonary bla...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.2830430211
更新日期:1993-06-01 00:00:00
abstract::We present a female patient with T-gamma LGL leukemia, who was followed for the last 20 years. Over these years she developed several autoimmune disorders, including Sjögren's syndrome, Hashimoto's thyroiditis, premature ovarian failure (compatible with type II autoimmune polyglandular syndrome), amegakaryocytic throm...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10024
更新日期:2002-02-01 00:00:00
abstract::A 74-year old woman with Ph1-negative chronic myelogenous leukemia (CML) and heterozygous for glucose-6-phosphate dehydrogenase (G6PD) was studied. Both A and B types of G6PD were found in skin. In contrast, white blood cells and platelets showed only a single G6PD type A. These results provide further evidence that P...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830170113
更新日期:1984-07-01 00:00:00
abstract::The value of menorrhagia as a predictor for mild bleeding disorders has been very little studied and the results are divergent. In the present study on 30 women with objectively verified menorrhagia, we found a significantly increased prevalence of von Willebrand's disease (20%). By keeping a strict sampling and labor...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(SICI)1096-8652(199612)53:4<234::AID-AJH4>
更新日期:1996-12-01 00:00:00
abstract::We report a case of T-cell chronic lymphoproliferative disorder (CLPD) that shows neither features of T-cell prolymphocytic leukemia nor disease progression for more than 34 months. Flow cytometric analyses of the lymphocytes revealed high expression of CD4 and CD25. Up-regulation of Foxp3, a master regulatory gene fo...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.20688
更新日期:2006-09-01 00:00:00
abstract::Cobalamin derivatives serve as coenzymes for the body's two cobalamin-dependent enzymes--adenosylcobalamin-dependent methylmalonyl CoA mutase, and methylcobalamin-dependent methionine methyltransferase. This essay reviews, in brief form and in personal terms, the history, beginning in the mid-1950s, of how these enzym...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.2830340203
更新日期:1990-06-01 00:00:00
abstract::Studies of in vitro chemotaxis and spontaneous migration of human leukocytes using the accepted method with the Boyden-chamber-filter are troublesome, because of the need for specially constructed vessels as well as the difficulties caused by the use of membrane filters. We describe a new and simplified method for mea...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830140308
更新日期:1983-05-01 00:00:00
abstract::The human spleen normally retains about one-third of the body's platelets in an exchangeable pool which can be released into the circulation by alpha-adrenergic stimulation. Some previous investigators concluded that the splenic platelet population was enriched in a subpopulation of large, young, dense platelets (mega...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830340302
更新日期:1990-07-01 00:00:00
abstract::Imatinib is currently the standard treatment for chronic myeloid leukemia(CML). Previous studies have shown that imatinib affects bone metabolism in CML patients. However, these effects are not well-studied prospectively. The authors studied bone-mineral density (BMD) and bone metabolism in 17 CML patients and matched...
journal_title:American journal of hematology
pub_type: 临床试验,杂志文章
doi:10.1002/ajh.23155
更新日期:2012-05-01 00:00:00
abstract::Recent literature has demonstrated concern over the risk of Pneumocystis jirovecii pneumonia (PJP) when administering rituximab with combination chemotherapy such as in R-CHOP; however, the exact risk and potential need for prophylaxis is unknown. We sought to determine the incidence of PJP infection following R-CHOP ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.24499
更新日期:2016-11-01 00:00:00
abstract::A patient is described who had blastic transformation of Ph1 negative chronic myelogenous leukemia (Ph1 - CML). Characterization of the leukemic cells revealed a population with a lymphoid stem cell phenotype (cALL-, TdT+, Ia+, cIgM-). This particular phenotype may be responsible for the refractoriness to vincristine ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830180211
更新日期:1985-02-01 00:00:00
abstract::The purpose of this study was to determine if therapeutic levels of Rituximab could be achieved in a patient with renal failure being dialyzed and if Rituximab is removed by hemodialysis. A 54-year-old man with low-grade lymphoma and renal failure on hemodialysis received 8 weekly treatments of Rituximab at 375 mg/M(2...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10213
更新日期:2002-11-01 00:00:00
abstract::Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830320105
更新日期:1989-09-01 00:00:00
abstract::Hypereosinophilic syndrome (HES) is a rare disorder that can manifest in various organ systems. We report the case of a 54-year-old woman with a remote history of seizure disorder who presented with early signs of right-sided heart failure. Laboratory studies showed significant eosinophilia (8 x 10(9) l(-1)). Computed...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.20933
更新日期:2007-10-01 00:00:00
abstract::Therapy-related acute myeloid leukemia (t-AML) arises as a late complication following antecedent solid tumors or hematologic diseases and their associated treatments. There are limited data regarding risk factors and outcomes following allogeneic hematopoietic cell transplantation (HCT) for t-AML following a prior so...
journal_title:American journal of hematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/ajh.25395
更新日期:2019-04-01 00:00:00