Contribution of Monoclonal Anti-T Cell Antibody in the Follow-Up and the Immunosuppressive Treatment of Renal Transplant Patients

Chatenoud, Lucienne; Baudrihaye, M.; Chkoff, N; Kreis, Henri; Bach, Jean‐François

doi:10.1007/978-1-4615-9358-4_28

Cited by 6 publications

(9 citation statements)

References 10 publications

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“…Whether the FcR and C3b receptors are independent in the in vivo situation studied here or whether the C3b or other receptors are quantitatively unimportant in the absence of effective FcR function remains to be determined. Antiidiotypic responses against injected murine antibodies have also been reported in humans (46,48). An antiidiotypic response, if capable of blocking the antibody-combining site, would prevent antibody-targeted particles from binding their target cells even if their circulation were prolonged.…”

Section: Discussionmentioning

confidence: 98%

Immune clearance of liposomes inhibited by an anti-Fc receptor antibody in vivo.

Aragnol¹,

Leserman²

1986

Proc. Natl. Acad. Sci. U.S.A.

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In a study designed to evaluate the potential for in vivo manipulation of the circulation and tissue distribution of injected liposomes, mice were passively injected with antidinitrophenyl (anti-DNP) monoclonal antibodies of the IgG2a or IgG2b subclasses or were immunized with the nitrophenyl hapten bound to a protein carrier. They were then injected i.v. with 12'I-and carboxyfluorescein-labeled, DNPbearing liposomes. Circulation time of the DNP-bearing liposomes was markedly reduced in actively and passively immune mice, with increased deposition of liposomes in the liver. The increased clearance of liposomes could be abrogated by injection of a monoclonal antibody directed against the murine IgG Fc receptor (2.4G2). The results suggest that clearance of ligand-bearing reagent in the face of an immune response may be modified by specific immunologic manipulation in vivo.

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Section: Discussionmentioning

confidence: 98%

Immune clearance of liposomes inhibited by an anti-Fc receptor antibody in vivo.

Aragnol¹,

Leserman²

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…While these antibody responses may be occurring too late to account for the absence of in vivo efficacy, the appearance of "neutralizing" antibodies may limit the temporal window during which these agents can be expected to exert their cytotoxic effect on the target cell population. Attempts to suppress the host's humoral response to infused murine monoclonal antibody through immunosuppressive drugs or radiation have had varied success (22,23). Sequential infusions with immunotoxins that bind to the same cell surface structure, but whose monoclonal antibody moiety is either not recognized as xenogeneic or is isotypically or idiotypically variant, and therefore not immediately "neutralized" by circulating antibodies, might serve to expand this window of potential treatment time.…”

mentioning

confidence: 99%

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. IV. Cytotoxic effect of an anti-T11-gelonin immunotoxin.

Reimann¹,

Goldmacher²,

Lambert³

et al. 1988

J. Clin. Invest.

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The cytotoxic effect of a lymphocyte-specific immunotoxin formed by disulfide conjugation of an anti-Ti 1 monoclonal antibody with the ribosome-inactivating protein gelonin was assessed in vitro on peripheral blood T cells and in vivo on splenic and lymph node T cells of macaque monkeys. This immunotoxin was cytotoxic to proliferating peripheral blood T cells in vitro as measured by both direct and indirect assays. Two sequential intravenous infusions into macaque monkeys achieved plasma concentrations of immunotoxin far in excess of those shown to be cytotoxic for cultured T cells and coated all T cells in lymph nodes and spleen with intact immunotoxin for four days. However, the cytotoxic effect of the immunotoxin on T cells in vivo was considerably less than that predicted by the in vitro studies. Further experiments suggested that the state of activation of the targeted T cell population in vivo, or the appearance of anti-immunotoxin antibodies, which occurred in all infused monkeys, might attenuate immunotoxin-mediated cell killing in vivo. These studies illustrate the significant differences between the action of immunotoxin conjugates in vitro, and those seen when these conjugates are utilized as therapeutic agents in vivo.

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“…Once again, the observed difference in sensitivity between these T cell subsets in the two experimental groups might reflect a difference in the affinity of the RhT3 antigen for the FN18 antibody. When OKT3, the anti-human homologue of FN18 in monkeys, is given to human graft recipients, it eliminates the CD3' population so rapidly [3,271 that it is impossible to differentiate between the elimination rate of the CD4' and CD8' subsets. However, a difference in the reappearance rate between these subsets was observed: CD4' cells return more quickly, resulting in a shift in the CD4/CD8 ratio.…”

Section: Discussionmentioning

confidence: 99%

The effect on skin allograft survival of a monoclonal antibody specific for a polymorphic CD3‐like cell surface molecule in rhesus monkeys

Nooij

Jonker

1987

Eur J Immunol

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FN18, a monoclonal antibody specific for the polymorphic rhesus monkey CD3 antigen on peripheral T cells, has been tested for its immunosuppressive effect in a rhesus monkey skin graft model. Animals were injected i.v. daily with antibody and they received an allogeneic skin graft two or three days after the initial antibody treatment. All animals were carefully monitored regarding levels of the major lymphocyte subsets. In animals in which RhT3 (a CD3-like antigen) is demonstrable (i.e. FN18+ phenotype), all T cells initially disappeared from the circulation. However, T cells without RhT3 on their surface reappeared after several days, indicating that these cells must have been modulated. The survival times of the skin grafts were significantly prolonged in these animals. In monkeys in which RhT3 is not demonstrable (i.e. FN18- phenotype), mainly part of the CD4+ lymphocyte subset was depleted. Although less explicit, skin graft survival was significantly prolonged in these animals as well. In both the FN18+ and FN18- groups a difference in sensitivity between the CD4+ and CD8+ cells for the FN18 antibody could be noticed. From the data it appears that FN18 is immunosuppressive and does not have serious side effects. The data are in agreement with information available for the use of OKT3 in clinical immunosuppression. Thus, extrapolation of data from the rhesus monkey model to the clinical situation seems feasible.

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Contribution of Monoclonal Anti-T Cell Antibody in the Follow-Up and the Immunosuppressive Treatment of Renal Transplant Patients

Cited by 6 publications

References 10 publications

Immune clearance of liposomes inhibited by an anti-Fc receptor antibody in vivo.

Immune clearance of liposomes inhibited by an anti-Fc receptor antibody in vivo.

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. IV. Cytotoxic effect of an anti-T11-gelonin immunotoxin.

The effect on skin allograft survival of a monoclonal antibody specific for a polymorphic CD3‐like cell surface molecule in rhesus monkeys

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