killer inhibitory receptor
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Hepatology ◽  
2011 ◽  
Vol 54 (5) ◽  
pp. 1559-1569 ◽  
Author(s):  
Lucy Golden-Mason ◽  
Kiran M. Bambha ◽  
Linling Cheng ◽  
Charles D. Howell ◽  
Milton W. Taylor ◽  
...  

2011 ◽  
Vol 85 (11) ◽  
pp. 5415-5422 ◽  
Author(s):  
S. Brackenridge ◽  
E. J. Evans ◽  
M. Toebes ◽  
N. Goonetilleke ◽  
M. K. P. Liu ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3015-3015
Author(s):  
N. Vey ◽  
J. Bourhis ◽  
H. Dombret ◽  
D. Bordessoule ◽  
T. Prebet ◽  
...  

3015 Background: The outcome of the majority of patients with AML remains poor, especially in the oldest patients. Allogeneic SCT is a curative approach for AML. In some models, it has been shown that KIR mismatch is important for the anti-leukemic effect of the graft, most probably through unleashed NK cells towards AML blasts, as suggested by enhanced in vitro NK lytic activity of KIR-HLA mismatched donor NK against recipient blasts. To mimic this effect with a pharmaceutical agent, a fully human IgG4 anti-KIR mAb specific for KIR2DL1/2/3 (HLA-C specific KIRs) was generated. We present the results of the first-in-human phase I trial of this agent in patients with AML in complete remission (CR). Methods: Patients aged 60–80 years with non promyelocytic AML in first CR following induction and 1–6 cycles of consolidation chemotherapy, normal renal, and hepatic functions, KIR-expression on patient NK-cells and who signed informed consent were eligible.Dose escalation (0.0003, 0.003, 0.015, 0.075, 0.3, 1, 3 mg/kg) was studied using a 3+3 scheme. Pharmacokinetic (PK) and circulating cytokines (MIP1β, TNF) were measured by ELISA. KIR occupancy and activation markers (CD69) were monitored by flow cytometry. Results: To date, inclusion has been completed until 1mg/kg cohort. Data of the first 15 patients (end of 0.3 mg/kg cohort) are available. No dose limiting toxicity has been observed. Side effects that could be related to drug administration were mild and transient. The first dose level resulted in a transient KIR occupancy ranging from 20 to 50%. PK values were then in line with modelling data, resulting at 0.3 mg/kg in a Cmax= 6350 ± 504 ng/mL, >80% KIR saturation for one week, and desaturation in the following week. As expected for an IgG4, NK cell numbers were unaffected by the treatment. Upregulation of CD69 on NK cells and concomitant increases in TNF and MIP1b circulating cytokines were observed in some patients at the highest doses (0.075, 0.1, 0.3 mg/kg) but a dose dependency has not been reached yet. Conclusions: Anti-KIR treatment is safe and well tolerated to date. At the 0.3mg/kg dose, MTD has not been reached, but a one week receptor blockade and signs of NK activation were observed. [Table: see text]


2003 ◽  
Vol 24 (4) ◽  
pp. 212-216 ◽  
Author(s):  
Mitsuhiro Takeno ◽  
Yoshihiro Shimoyama ◽  
Jun-Ichi Kashiwakura ◽  
Hiroko Nagafuchi ◽  
Tsuyoshi Sakane ◽  
...  

2002 ◽  
Vol 81 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Gaëlle Perrin ◽  
Daniel Speiser ◽  
Andrée Porret ◽  
Anne-Lise Quiquerez ◽  
Paul R Walker ◽  
...  

2002 ◽  
Vol 77 (2) ◽  
pp. 297-302 ◽  
Author(s):  
Nagamasa Maeda ◽  
Chiaki Izumiya ◽  
Yorito Yamamoto ◽  
Hiroyoshi Oguri ◽  
Tomoaki Kusume ◽  
...  

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