- In vitro Evidence That Combination Therapy With CD16-Bearing NK-92 Cells and FDA-Approved Alefacept Can Selectively Target the Latent HIV Reservoir in CD4+ CD2hi Memory T Cells. [Journal Article]
- FIFront Immunol 2018; 9:2552
- Elimination of the latent HIV reservoir remains the biggest hurdle to achieve HIV cure. In order to specifically eliminate HIV infected cells they must be distinguishable from uninfected cells. CD2 w...
Elimination of the latent HIV reservoir remains the biggest hurdle to achieve HIV cure. In order to specifically eliminate HIV infected cells they must be distinguishable from uninfected cells. CD2 was recently identified as a potential marker enriched in the HIV-1 reservoir on CD4+ T cells, the largest, longest-lived and best-characterized constituent of the HIV reservoir. We previously proposed to repurpose FDA-approved alefacept, a humanized α-CD2 fusion protein, to reduce the HIV reservoir in CD2hi CD4+ memory T cells. Here, we show the first evidence that alefacept can specifically target and reduce CD2hi HIV infected cells in vitro. We explore a variety of natural killer (NK) cells as mediators of antibody-dependent cell-mediated cytotoxicity (ADCC) including primary NK cells, expanded NK cells as well as the CD16 transduced NK-92 cell line which is currently under study in clinical trials as a treatment for cancer. We demonstrate that CD16.NK-92 has a natural preference to kill CD2hi CD45RA- memory T cells, specifically CD45RA- CD27+ central memory/transitional memory (TCM/TM) subset in both healthy and HIV+ patient samples as well as to reduce HIV DNA from HIV+ samples from donors well controlled on antiretroviral therapy. Lastly, alefacept can combine with CD16.NK-92 to decrease HIV DNA in some patient samples and thus may yield value as part of a strategy toward sustained HIV remission.
- Systemic treatments for alopecia areata: A systematic review. [Review]
- AJAustralas J Dermatol 2018 Sep 06
- A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopec...
A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopecia areata, alopecia totalis and alopecia universalis. A systematic search was conducted of the peer-reviewed literature published between 1946 and March 2018 via Medline, Embase, Amed, the Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All randomised controlled trials (RCTs) that evaluated the effectiveness of systemic treatments for individuals with alopecia areata, totalis or universalis were included. Sixteen studies were included with a total of 768 participants. We found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments and five RCTs comparing three treatments. A total of 15 different systemic therapies were investigated. The most frequently investigated therapy was oral prednisolone pulse therapy and oral inosiplex. There was significant variability in the definition of treatment success. No study evaluated the impact of pharmacotherapy on quality of life using complete quantitative quality of life instruments. Adverse events were reported in 13 studies and were corticosteroid related or otherwise well tolerated. Relapse rates were considerable in the four studies that reported this outcome. There is currently no specific systemic therapy that is supported by robust body of evidence from RCTs. The current evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex. Evidence does not support the use of oral zinc sulphate, alefacept and efalizumab. Future RCTs should be adequately powered and employ clearly defined clinical response endpoints to allow future meta-analyses.
- ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors). [Consensus Development Conference]
- CMClin Microbiol Infect 2018; 24 Suppl 2:S95-S107
- CONCLUSIONS: Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.
- Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. [Review]
- CDCochrane Database Syst Rev 2017 12 22; 12:CD011535
- CONCLUSIONS: Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.
- Old and New Biological Therapies for Psoriasis. [Review]
- IJInt J Mol Sci 2017 Nov 01; 18(11)
- Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised small molecule drugs, targeting...
Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised small molecule drugs, targeting the immune system in a non-specific manner. The first biologics targeted T-cell activation and migration and served as an alternative to small molecules. However, significant improvement in outcome was first accomplished with the introduction of tumor necrosis factor-α inhibitors that were already approved for other inflammatory disorders, including rheumatic diseases. Along with the progress in understanding psoriasis pathogenesis, highly targeted and effective therapies have since developed with the perspective not only to improve but to clear psoriasis. These accomplishments enable future achievement of advanced goals to individualize treatment best suited for each patient. Mechanistic studies with patients treated with the new highly targeted biologics may guide us towards these goals. This review offers an overview of biologics developed for psoriasis and illustrate a historical progress in the treatment of this common chronic inflammatory skin condition.
- Anti‑cytokine therapy for psoriasis - not only TNF‑α blockers. Overview of reports on the effectiveness of therapy with IL‑12/IL‑23 and T and B lymphocyte inhibitors. [Review]
- PHPostepy Hig Med Dosw (Online) 2016 Dec 08; 70(0):1198-1205
- TNF‑α inhibitors - infliximab, etanercept and adalimumab - can be used in the treatment of psoriasis vulgaris and psoriatic arthritis, along with other inhibitors of proinflammatory cytokines, such a...
TNF‑α inhibitors - infliximab, etanercept and adalimumab - can be used in the treatment of psoriasis vulgaris and psoriatic arthritis, along with other inhibitors of proinflammatory cytokines, such as interleukin‑12 (IL‑12) and IL‑23. This paper presents the results of research on the use of biological drugs other than the tumor necrosis factor blockers (TNF‑α), namely inhibitors of IL‑12 and IL‑23 (ustekinumab), T‑cell inhibitors (alefacept and efalizumab), B‑cell inhibitors (rituximab), anti‑IL‑17 agents (secukinumab, ixekizumab, and brodalumab) and IL23p19 inhibitors (guselkumab and tildrakizumab). The paper presents an analysis of the mechanism of action, recommended doses and methods of therapy, taking into account the adverse events associated with the use of anti‑cytokine therapy. The use of biological drugs is discussed based on a review of the current literature.
- Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude. [Review]
- HHomeopathy 2016; 105(4):344-355
- CONCLUSIONS: As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism).
- Can restoring immune balance be the ultimate therapy for type 1 diabetes? [Journal Article]
- JDJ Diabetes Investig 2016; 7(6):819-821
- Graft Versus Host Disease After Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management. [Case Reports]
- TTransplantation 2016; 100(12):2661-2670
- CONCLUSIONS: Age older than 50 years and hepatocellular carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High-dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD after LT. CD2-blockers and TNF-α antagonists appear promising. We propose a diagnostic algorithm to assist clinicians in managing adults with GVHD after LT.
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- Correlation Among Hypoglycemia, Glycemic Variability, and C-Peptide Preservation After Alefacept Therapy in Patients with Type 1 Diabetes Mellitus: Analysis of Data from the Immune Tolerance Network T1DAL Trial. [Randomized Controlled Trial]
- CTClin Ther 2016; 38(6):1327-1339
- In natural history studies, maintenance of higher levels of C-peptide secretion (a measure of endogenous insulin production) correlates with a lower incidence of major hypoglycemic events in patients...
In natural history studies, maintenance of higher levels of C-peptide secretion (a measure of endogenous insulin production) correlates with a lower incidence of major hypoglycemic events in patients with type 1 diabetes mellitus (T1D), but it is unclear whether this is also true for drug-induced C-peptide preservation.