A Phase I-Ii Study Evaluating the Murine Anti-Il-2 Receptor Antibody 2a3 for Treatment of Acute Graft-Versus-Host Disease

Anasetti, Claudio; Martin, Paul J.; Hansen, John A.; Appelbaum, Frederick R.; Beatty, Patrick G.; Doney, Kristine; Harkonen, Scott; Jackson, Anne L.; Reichert, Tom; Stewart, Patricia; Storb, R; Sullivan, Keith M.; Thomas, E. D.; Warner, Noel L.; Witherspoon, Robert P.

doi:10.1097/00007890-199007000-00010

Cited by 55 publications

(22 citation statements)

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“…Similar results were also reported by Kumaki et al 18 and Imamura et al 32 This can be explained by the dramatically decreased number of T cells, which are a rich source of IL-2, after pretransplant conditioning. Moreover, in human trials, neutralizing antibodies against IL-2 or the IL-2 receptor ␣ chain were unable to eliminate GVHD, 33,34 suggesting that a cytokine other than IL-2 controls the effector cells. IL-15 which was significantly elevated in the severe aGVHD group, is one of the candidates for control of the effector cells because IL-15 has many overlapping biological activities with IL-2, such as costimulation of T cell proliferation and induction of cytotoxic activity of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease

Sakata

Yasui

Okamura

et al. 2001

Bone Marrow Transplant

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Summary:The plasma levels of a panel of cytokines and cytokineassociated molecules (IL-1␣, IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, macrophage colony-stimulating factor (M-CSF), interferon-␥ (IFN-␥), tumor necrosis factor-␣ (TNF-␣), soluble IL-2 receptor (sIL-2R), soluble tumor necrosis factor receptor I or II (sTNFRI or II)) were assessed in 56 plasma samples of 13 pediatric patients undergoing hematopoietic stem cell transplantation (HSCT, bone marrow in 12 and cord blood in one) from unrelated donors. Eight patients developed severe (grade III-IV) acute GVHD (aGVHD). The plasma IL-6, IL-10, M-CSF, sTNFRI and II levels were significantly high in the severe aGVHD group compared to the mild aGVHD group (grade 0-II). The plasma IL-15 level increased transiently in the early period following HSCT and remained high in the severe aGVHD group even after 4 weeks following HSCT. Based on analysis of the correlations between the kinetics of the plasma cytokine levels after HSCT and the clinical manifestations of aGVHD, IL-15 and/or M-CSF were involved in the development of aGVHD, following elevation of the plasma IL-10 and sTNFRI or II levels. These kinetics suggest that IL-10 and sTNFRs worked as suppressor cytokines and seemed to suppress clinical manifestations of aGVHD. Furthermore, it seemed that the plasma ratio of IL-10/sTNFRII from 5 to 12 weeks following HSCT was linked to the poor outcome in the patients with severe aGVHD, suggesting that IL-10 plays an important role in protecting hosts from transplantation-related complications, including GVHD.

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Section: Discussionmentioning

confidence: 99%

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease

Sakata

Yasui

Okamura

et al. 2001

Bone Marrow Transplant

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“…High levels of soluble IL-2R have been demonstrated in patients with acute GVHD, 16 and anti-IL-2R antibodies have been effective in treating GVHD. [17][18][19][20] However, several studies of IL-2 in humans failed to show an alteration in IL-2 expression at either the protein level or the mRNA level 21,22 and only one study detected IL-2 expression more frequently in patients with acute GVHD than in those without GVHD. 23 Thus, our report is the first to show a quantitative alteration in the levels of IL-2 gene expression during the development of clinical GVHD.…”

Section: Discussionmentioning

confidence: 99%

Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion

Das¹,

Imoto²,

Murayama³

et al. 2001

Bone Marrow Transplant

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“…In these cases, GVHD appeared again after once GVHD was improved according to the intensified immunosuppressive treatment. Considering that IL2/IL2R system is important in acute GVHD [26,27], this indicates that early and late increases of granulysin after allogeneic SCT are based on the different settings. According to the observation by Sarwal et al [22], granulysin production from long-term CTL is steroid-insensitive and paradoxically increased by CSP treatment.…”

Section: Discussionmentioning

confidence: 99%

“…IL2 [26,27] and IFN-g [28,29] are involved in the pathogenesis of GVHD. To evaluate the relation of sIL2R and IFN-g with granulysin, the correlation coefficient index was calculated.…”

Section: Serum Granulysin Level Is Not Necessarily Correlated With Sementioning

confidence: 99%

Analysis of serum granulysin in patients with hematopoietic stem‐cell transplantation: Its usefulness as a marker of graft‐versus‐host reaction

et al. 2006

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Granulysin is a newly identified CTL/NK cell-related cytotoxic protein, which is secreted in both constitutive and Ca-dependent manner. To evaluate its significance in stem-cell transplantation (SCT), serum granulysin was measured by newly established ELISA method in 26 patients undergoing SCT (21 allogeneic and 5 autologous). In the allogeneic SCT, granulysin was transiently increased in 3 weeks, which was not observed in autologous SCT. In acute GVHD, serum granulysin was markedly increased and correlated with the severity of GVHD. Elevation of granulysin was not necessarily associated with increase of sIL2R or IFN-g. In vitro, allospecific T cells released granulysin in an allo-specific manner, and it was correlated with allo-specific cytotoxic activity. These results indicate that increased release of granulysin presents alloreactivity and serum granulysin is useful as a marker of GVHD in SCT. Am. J.

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A Phase I-Ii Study Evaluating the Murine Anti-Il-2 Receptor Antibody 2a3 for Treatment of Acute Graft-Versus-Host Disease

Cited by 55 publications

References 0 publications

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease

Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion

Analysis of serum granulysin in patients with hematopoietic stem‐cell transplantation: Its usefulness as a marker of graft‐versus‐host reaction

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