Inhibition of corneal allograft reaction by CTLA4-Ig

Hoffmann, Friedrich; Zhang, Er-Ping; Pohl, Thomas; Kunzendorf, Ulrich; Wachtlin, Joachim; Bulfone–Paus∥, Silvia

doi:10.1007/bf00947013

Cited by 25 publications

(23 citation statements)

References 29 publications

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“…Recombinant adenovirus (Ad)-mediated gene transfer is an excellent strategy for both local and systemic gene therapy because of its high transduction efficiency to various cell types and organs [20]. Recently, the blockade of CD28-B7 interaction by a chimeric CTLA4Ig fusion protein has been shown to be an efficient therapy to prevent corneal allograft rejection [21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

The influence of inducible costimulator fusion protein (ICOSIg) gene transfer on corneal allograft survival

Fabián

Gong

Vogt

et al. 2007

Graefes Arch Clin Exp Ophthalmol

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Section: Introductionmentioning

confidence: 99%

The influence of inducible costimulator fusion protein (ICOSIg) gene transfer on corneal allograft survival

Fabián

Gong

Vogt

et al. 2007

Graefes Arch Clin Exp Ophthalmol

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“…Complete and effective activation of T cells is contingent upon binding of T cell receptor/CD3 with MHC molecules on APCs, and interaction of T cell co-stimulatory molecule CD28 with B7 antigens on APCs (CD80 and CD86) [180]. Cytotoxic T-Lymphocyte Antigen 4 protein (CTLA4-Ig), a fusion protein that competitively inhibits the binding of B7 antigens with CD28, inhibits the activation of T cells and has been shown to prolong corneal allograft survival after systemic injections or gene delivery to the corneal epithelium [181,182]. Systemic administration of anti-CD28 monoclonal antibody or local administration of non-functional CTLA4-Ig in rats, has also demonstrated prolonged graft survival [183].…”

Section: Therapies For Corneal Graft Rejectionmentioning

confidence: 99%

Corneal Allograft Rejection: Immunopathogenesis to Therapeutics

Qazi

Hamrah²

2013

J Clin Cell Immunol

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Corneal transplantation is among the most successful solid organ transplants. However, despite low rejection rates of grafts in the ‘low-risk’ setting, rejection can be as high as 70% when grafted into ‘high-risk’ recipient beds. Under normal homeostatic conditions, the avascular cornea provides a unique environment that facilitates immune and angiogenic privilege. An imbalance in pro-inflammatory, angiogenic and lymphangiogenic mediators leads to a breakdown in corneal immune privilege with a consequent host response against the donor graft. Recent developments in lamellar and endothelial keratoplasties have reduced the rates of graft rejection even more, while providing improved visual outcomes. The corneal layer against which an immune response is initiated, largely determines reversibility of the acute episode. While epithelial and stromal graft rejection may be treated with topical corticosteroids with higher success, acute endothelial rejection mandates a more aggressive approach to therapy due to the lack of regenerative capacity of this layer. However, current immunosuppressive regimens come with the caveat of ocular and systemic side effects, making prolonged aggressive treatment undesirable. With the advent of biologics, efficacious therapies with a superior side effect profile are on the horizon. In our review we discuss the mediators of ocular immune privilege, the roles of cellular and molecular immune players in graft rejection, with a focus on human leukocyte antigen and antigen presenting cells. Furthermore, we discuss the clinical risk factors for graft rejection and compare rates of rejection in lamellar and endothelial keratoplasties to traditional penetrating keratoplasty. Lastly, we present the current and upcoming measures of therapeutic strategies to manage and treat graft rejection, including an overview of biologics and small molecule therapy.

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“…CTLA4-Ig is a recombinant form of CTLA4 that acts as a competitive inhibitor of this CD28–CD80–CD86 pathway. Gene-based administration of CTLA4-Ig has shown promise in prolonging allograft survival in animal models 73107–8. Comer and colleagues73 described suppression of CD80 and CD28 expression using adenovirus-mediated delivery of CD80 mRNA into Brown Norway rat corneas, which were subsequently grafted into Lewis rat recipients.…”

Section: Gene Therapymentioning

confidence: 99%

Strategies for local gene therapy of corneal allograft rejection

Nguyẽ̂n¹,

Yiu²

2013

Middle East Afr J Ophthalmol

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Penetrating keratoplasty is the most common type of tissue transplant in humans. Irreversible immune rejection leads to loss of vision and graft failure. This complex immune response further predisposes future corneal transplants to rejection and failure. A diverse armamentarium of surgical and pharmacologic tools is available to improve graft survival. In this review, we will discuss the various gene therapeutic strategies aimed at potentiating the anterior chamber-associated immune deviation to extend graft survival.

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Inhibition of corneal allograft reaction by CTLA4-Ig

Cited by 25 publications

References 29 publications

The influence of inducible costimulator fusion protein (ICOSIg) gene transfer on corneal allograft survival

The influence of inducible costimulator fusion protein (ICOSIg) gene transfer on corneal allograft survival

Corneal Allograft Rejection: Immunopathogenesis to Therapeutics

Strategies for local gene therapy of corneal allograft rejection

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