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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Transplant
2014 ; 14
(6
): 1346-55
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First-in-human study of the safety and efficacy of TOL101 induction to prevent
kidney transplant rejection
#MMPMID24751150
Flechner SM
; Mulgoankar S
; Melton LB
; Waid TH
; Agarwal A
; Miller SD
; Fokta F
; Getts MT
; Frederick TJ
; Herrman JJ
; Puisis JP
; O'Toole L
; Sung R
; Shihab F
; Wiseman AC
; Getts DR
Am J Transplant
2014[Jun]; 14
(6
): 1346-55
PMID24751150
show ga
TOL101 is a murine IgM mAb targeting the ?? TCR. Unlike other T cell targets, the
?? TCR has no known intracellular signaling domains and may provide a
nonmitogenic target for T cell inactivation. We report the 6-month Phase 2 trial
data testing TOL101 in kidney transplantation. The study was designed to identify
a dose that resulted in significant CD3 T cell modulation (<25 T cell/mm(3) ), to
examine the safety and tolerability of TOL101 and to obtain preliminary efficacy
information. Thirty-six patients were enrolled and given 5-10 daily doses of
TOL101; 33 patients completed dosing, while three discontinued after two doses
due to a self-limiting urticarial rash. Infusion adjustments, antihistamines,
steroids and dose escalation of TOL101 reduced the incidence of the rash. Doses
of TOL101 above 28 mg resulted in prolonged CD3 modulation, with rapid recovery
observed 7 days after therapy cessation. There were no cases of patient or graft
loss. Few significant adverse events were reported, with one nosocomial
pneumonia. There were five biopsy-confirmed acute cellular rejections (13.9%);
however, no donor-specific antibodies were detected. Overall TOL101 was
well-tolerated, supporting continued clinical development using the dose
escalating 21-28-42-42-42 mg regimen.
|*Kidney Transplantation/adverse effects
[MESH]
|Adult
[MESH]
|Antibodies, Monoclonal, Murine-Derived/*therapeutic use
[MESH]