Nonhuman Primate Responses to Murine and Humanized Okt4a

Delmonico, Francis L.; Cosimi, A. Benedict; Kawai, T; Cavender, Druie; Lee, Woan-Hwa; Jolliffe, Linda K.; Knowles, Robert W.

doi:10.1097/00007890-199304000-00007

Cited by 24 publications

(6 citation statements)

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“…This effect has been seen before in monkeys given the humanized anti-CD4 mAb OKTcdr4a (41); however, this mAb was not immunogenic in patients (38). We recognize that our blocking assay could be affected by anti-constant region antibodies (47), as other assays may also be affected (41). In fact, we have shown that some of the monkey sera did have antibodies that prevented the binding of a totally unrelated human anti-CD4 mAb that shares no known V region sequence homologies, idiotypes, or antigenic fine specificity.…”

Section: Discussionsupporting

confidence: 67%

Differential Effects of Administration of a Human Anti-CD4 Monoclonal Antibody, HM6G, in Nonhuman Primates

Fishwild¹,

Hudson²,

Deshpande³

et al. 1999

Clinical Immunology

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Section: Discussionsupporting

confidence: 67%

Differential Effects of Administration of a Human Anti-CD4 Monoclonal Antibody, HM6G, in Nonhuman Primates

Fishwild¹,

Hudson²,

Deshpande³

et al. 1999

Clinical Immunology

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“…These early monoclonal antibodies, namely OKT3, although effective at treating acute rejection, were associated with cytokine release syndrome, increased risk of posttransplant lymphoproliferative disease, and xenosensitization to its murine component (Chatenoud et al 1990;Schroeder et al 1990;Cherikh et al 2003). To diminish the antimurine response, humanized chimeric preparations of several of the early monoclonal antibodies were developed and are still used in nonhuman primate studies today (Woodle et al 1992;Delmonico et al 1993;Engram et al 2010).…”

Section: Other T-cell Depleting Agentsmentioning

confidence: 99%

Lymphodepletional Strategies in Transplantation

Page

Kwun

et al. 2013

Cold Spring Harbor Perspectives in Medicine

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Because lymphocytes were shown to mediate transplant rejection, their depletion has been studied as a mechanism of preventing rejection and perhaps inducing immunologic tolerance. Agents that profoundly deplete lymphocytes have included monoclonal antibodies, cytotoxic drugs, and radiation. We have studied several such agents but focused on antibodies that deplete not only peripheral blood lymphocytes, but also lymph node lymphocytes. Depletion of lymph node T lymphocytes appears to permit peripheral tolerance at least for T cells in animal models. Nevertheless, B-cell responses may be resistant to such approaches, and T memory cells are likewise relatively resistant to depleting antibodies. We review the experimental and clinical approaches to depletion strategies and outline some of the pitfalls of depletion, such as limitations of currently available agents, duration of tolerance, infection, and malignancy. It is notable that most tolerogenic strategies that have been attempted experimentally and clinically include depleting agents even when they are not named as the underlying strategy. Thus, there is an implicitly acknowledged role for reducing the precursor frequency of donor antigen-specific lymphocytes when approaching the daunting goal of transplant tolerance.

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“…However, autologous antibodies can be induced against a variety of fully human biological agents that are used for therapy (39)(40)(41)(42)(43)(44)(45)(46). Depending on their epitope specificity, autoreactive anti-CD4 antibodies have been shown to mediate CD4 ϩ T cell depletion, suppression of T cell-dependent immune responses, or various other forms of immune dysregulation (47)(48)(49)(50)(51)(52)(53)(54), effects that define safety concerns for HIV vaccine testing.…”

mentioning

confidence: 99%

An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

Schwartz

Prado

Misamore

et al. 2016

Clin Vaccine Immunol

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؉ T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4 ؉ T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures are unlikely to elicit autoimmune antibody responses, supporting the advancement of gp120-CD4 complexbased antigens, such as FLSC, into clinical testing.

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Nonhuman Primate Responses to Murine and Humanized Okt4a

Cited by 24 publications

References 0 publications

Differential Effects of Administration of a Human Anti-CD4 Monoclonal Antibody, HM6G, in Nonhuman Primates

Differential Effects of Administration of a Human Anti-CD4 Monoclonal Antibody, HM6G, in Nonhuman Primates

Lymphodepletional Strategies in Transplantation

An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

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