PMID- 27110598
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2471-9552 (Print)
IS  - 2471-9552 (Linking)
VI  - 1
IP  - 1
DP  - 2015 Dec
TI  - Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?
LID - 104 [pii]
AB  - 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 cell-mediated 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 CD2(hi) memory 
      CD4(+) T cells are a significant contributor.
FAU - Zaidi, Asifa
AU  - Zaidi A
AD  - Department of Dermatology, Case Western Reserve University School of Medicine, 
      Cleveland, OH 44106, USA.
FAU - Meng, Qinglai
AU  - Meng Q
AD  - Department of Dermatology, Case Western Reserve University School of Medicine, 
      Cleveland, OH 44106, USA.
FAU - Popkin, Daniel
AU  - Popkin D
AD  - Department of Dermatology, Case Western Reserve University School of Medicine, 
      Cleveland, OH 44106, USA.
LA  - eng
GR  - P30 AI027767/AI/NIAID NIH HHS/United States
GR  - P30 AR039750/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20151130
PL  - United States
TA  - Immunotherapy (Los Angel)
JT  - Immunotherapy (Los Angeles, Calif.)
JID - 101676003
PMC - PMC4841618
MID - NIHMS755163
OTO - NOTNLM
OT  - ADCC
OT  - Alefacept
OT  - CD4+ T cells
OT  - HIV reservoir
OT  - NK cells
EDAT- 2016/04/26 06:00
MHDA- 2016/04/26 06:01
PMCR- 2016/04/22
CRDT- 2016/04/26 06:00
PHST- 2016/04/26 06:00 [entrez]
PHST- 2016/04/26 06:00 [pubmed]
PHST- 2016/04/26 06:01 [medline]
PHST- 2016/04/22 00:00 [pmc-release]
AID - 104 [pii]
AID - 10.4172/imt.1000104 [doi]
PST - ppublish
SO  - Immunotherapy (Los Angel). 2015 Dec;1(1):104. doi: 10.4172/imt.1000104. Epub 2015 
      Nov 30.