In Vivo Cell Activation Following Okt3 Administration

Chatenoud, Lucienne; Ferran, Christiane; Legendre, Christophe; Thouard, Isabelle; Merite, Sylvie; Reuter, A.; Gevaert, Y.; Kreis, Henri; Franchimont, P; Bach, Jean‐François

doi:10.1097/00007890-199004000-00009

Cited by 303 publications

(46 citation statements)

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“…In this study, acute GVHD was more common among patients treated with OKT-3 during pre-transplant conditioning. OKT-3 also resulted in a massive release of inflammatory cytokines, including TNF-␣, 35 which may be involved in the induction of GVHD. This may explain the high incidence of more severe acute GVHD after OKT-3 treatment, as other known risk factors for acute GVHD such as herpes virus status, female donor to male recipient, HLA match and GVHD prophylaxis 28,36 were similar in patients treated with ATG-F, Thymoglobuline and OKT-3 (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation

Remberger

Svahn

Hentschke

et al. 1999

Bone Marrow Transplant

123

115

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Summary:Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-␥, TNF-␣ and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose у2.7 ؋ 10 8 /kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMGpatients and 43% (P Ͻ 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.

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Section: Discussionmentioning

confidence: 99%

Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation

Remberger

Svahn

Hentschke

et al. 1999

Bone Marrow Transplant

123

115

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“…As pre-treatment with high-dose steroids has been reported to decrease toxicity of IgG2a anti-CD3 mAb in mice and men (6,8,(36)(37)(38)(39), it is tempting to speculate that omitting pre-treatment with steroids would even have increased the difference in toxicity and cytokine profile ofT3.A and T3.G2a. Interesting is the occurrence ofchills and TNF release after the first administration of T3.A.…”

Section: Methodsmentioning

confidence: 99%

In vivo effects of IgA and IgG2a anti-CD3 isotype switch variants.

Parlevliet

Berge²,

Yong³

et al. 1994

J. Clin. Invest.

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Side effects after the first administration of OKT3, a murine anti-CD3 monoclonal antibody (mAb) of the IgG2a class, are largely attributed to the release of cytokines as a result ofT cell activation caused by interaction with Fc receptors (FcR) on human monocytes. As human monocytes possess FcR for murine IgG2a but not for IgA, it is expected that an anti-CD3 mAb of the IgA class causes less side-effects than an IgG2a anti-CD3 mAb of the same idiotype. To test this hypothesis we treated 20 renal transplant patients prophylactically with either IgG2a or IgA anti-CD3 mAb in a prospective randomized double-blind study. The patients received 0.5 mg anti-CD3 mAb, either IgA (T3.A) or IgG2a (T3.G2a), twice daily during 10 d. Rejection incidence after T3.A and T3.G2a was not significantly different. Side effects score after the first administration of mAb was significantly less after T3.A than after T3.G2a (0.7 vs 2.7, P = 0.002). IL-6 and gamma IFN levels increased significantly at 3 h after T3.G2a, but not after T3.A. The TNF peak level occurring at 1 h after T3.A was much lower than after T3.G2a. In plasma, complement and neutrophil activation products only increased after T3.G2a and not after T3.A. Both T3.A and T3.G2a resulted in a complete depletion of CD3+ cells, but after T3.A, CD3 depletion was of shorter duration than after IgG2a. Finally, in contrast to T3.G2a, T3.A did not affect coagulation and fibrinolysis. In conclusion, an anti-CD3 mAb of the IgA class causes hardly any cytokine release and less side-effects as compared with its IgG2a switch variant. Provided T3.A is sufficiently immunosuppressive, it is superior to OKT3. (J.

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“…These observations are even more curious since the half-life of infused TNF is quite short. Certainly, the induction of TNF in humans by endotoxin or OKT3 (in transplantation) is transient [4,19]. However, in these reports, there was not a repetitive induction signal being delivered to the patient.…”

Section: Discussionmentioning

confidence: 97%

Production of tumor necrosis factor α and interferon γ in interleukin-2-treated melanoma patients: Correlation with clinical toxicity

Economou

Hoban

Lee

et al. 1991

Cancer Immunol Immunother

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Interleukin-2 (IL-2)-based immunotherapy regimens are accompanied by dose-limiting toxicity consisting of fever, tachycardia, chills and capillary leak syndrome. We hypothesized that the toxicity was caused by the induction and release of endogenous cytokines such as tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). We measured the serum levels of TNF alpha and IFN gamma in IL-2-treated melanoma patients and attempted a correlation with clinical toxicity. A total of 23 patients received either 6 x 10(6) IU or 12 x 10(6) IU Cetus IL-2/m2 by i.v. bolus daily for 5 consecutive days on weeks 1, 3 and 5. Serum TNF alpha and IFN gamma levels were measured by enzyme-linked immunosorbent assay. Clinical toxicity was scored each day by objective measurements of hypotension, tachycardia, fever and chills/rigors. Clinical toxicity and IFN gamma levels correlated nicely, peaking on the 5th day of each treatment cycle. The kinetics and magnitude of TNF alpha production, however, were not predictable and did not correlate with either IFN gamma or toxicity. Some patients had modest increases in TNF alpha production while others had markedly increased levels during the second and third treatment weeks. Remarkably, these high levels persisted during nontreatment weeks and after completion of therapy. This clinical study demonstrates novel kinetics for immunoreactive TNF alpha in IL-2 cancer patients, which do not correlate well with toxicity.

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In Vivo Cell Activation Following Okt3 Administration

Cited by 303 publications

References 0 publications

Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation

Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation

In vivo effects of IgA and IgG2a anti-CD3 isotype switch variants.

Production of tumor necrosis factor α and interferon γ in interleukin-2-treated melanoma patients: Correlation with clinical toxicity

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