Prophylaxis of graft-versus-host disease by administration of the murine anti-IL-2 receptor antibody 2A3.
The efficacy of murine monoclonal IgG1 antibody 2A3 specific for the 55 kD chain of the human IL-2 receptor (CD25) was evaluated for prophylaxis of acute GVHD in patients with advanced leukemia transplanted with unmodified bone marrow from related HLA-haploidentical donors incompatible for two or three HLA loci of the nonshared haplotype. As GVHD prophylaxis, 36 patients (control) received standard cyclosporine and methotrexate (C + M) whereas 11 patients (study) received C + M plus antibody 2A3, 1.0 mg/kg on day -1, and 0.5 mg/kg daily from day 0 through day +19. Antibody administration was not associated with appreciable toxicity and did not adversely affect engraftment. During treatment, circulating CD25+ cells appeared saturated by the infused antibody. Patients receiving antibody 2A3 tolerated more cyclosporine than controls (p less than 0.001) with lower increase of serum creatinine (p less than 0.05) during the first month. Seven of 10 (70%) evaluable study patients developed acute GVHD of grade II-IV with onset at a median of 20 days compared to 27 of 31 (87%) control patients with onset at a median of 13 days (p = 0.11). Trough serum levels of antibody 2A3 ranged from 7.2 to 68.8 mg/l, and lower values correlated with occurrence of acute GVHD. A human anti-mouse immunoglobulin antibody response was detected in four patients but was not associated with lower levels of antibody 2A3 in the serum. Two study patients and two controls have survived more than 1 year (p = 0.92). These findings suggest that administration of antibody 2A3 suppressed and delayed activation of alloantigen-specific T cells but did not result in their elimination.
Anasetti
C
C
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Martin
P J
PJ
Storb
R
R
Appelbaum
F R
FR
Beatty
P G
PG
Calori
E
E
Davis
J
J
Doney
K
K
Reichert
T
T
Stewart
P
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D007938:Leukemia / Q000401:mortality / Q000601:surgery; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2