alexa Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?
ISSN: 2471-9552

Immunotherapy: Open Access
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Review Article

Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

Asifa Zaidi*, Qinglai Meng* and Daniel Popkin*

Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA

*Corresponding Author:
Asifa Zaidi
Department of Dermatology
Case Western Reserve University School of Medicine
Cleveland, OH 44139, USA
Tel: 216-368-1303
E-mail: [email protected]
Qinglai Meng
Department of Dermatology
Case Western Reserve University School of Medicine
Cleveland, OH 44139, USA
Tel: 216-368-1303
E-mail: [email protected]
Daniel Popkin
Department of Dermatology
Case Western Reserve University School of Medicine
Cleveland, OH 44139, USA
Tel: 216-368-1303
E-mail: [email protected]

Received date: October 21, 2015 Accepted date: November 26, 2015 Published date: November 30, 2015

Citation: Zaidi A, Meng Q, Popkin D (2015) Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?. Immunother open access 1:104. doi:10.4172/2471-9552.1000104

Copyright: © 2015 Zaidi A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Current anti-retroviral treatment (ART) for HIV is effective in maintaining HIV at undetectable levels. However, cessation of ART results in immediate and brisk rebound of viremia to high levels. This rebound is driven by an HIV reservoir mainly enriched in memory CD4+ T cells. In order to provide any form of functional HIV Cure, elimination of this viral reservoir has become the focus of current HIV cure strategies. Alefacept was initially developed for the treatment of chronic plaque psoriasis. Alefacept is a chimeric fusion protein consisting of the CD2-binding portion of human leukocyte function antigen-3 (LFA3) linked to the Fc region of human IgG1 (LFA3-Fc). Alefacept was designed to inhibit memory T cell activation that contributes to the chronic autoimmune disease psoriasis by blocking the CD2 coreceptor. However, it was found to deplete memory T cells that express high levels of CD2 via NK cellmediated antibody dependent cell cytotoxicity (ADCC) in vivo. Phase II and phase III clinical trials of alefacept with psoriasis patients demonstrated promising results and an excellent safety profile. Subsequently, alefacept has been successfully repurposed for other memory T cell-mediated autoimmune diseases including skin diseases other than psoriasis, organ transplantation and type I diabetes (T1D). Herein, we review our specific strategy to repurpose the FDA approved biologic alefacept to decrease and hopefully someday eliminate the HIV reservoir, for which CD2hi memory CD4+ T cells are a significant contributor.

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