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Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Experimental research seeking a way to treat autoimmune disease without disrupting normal immune activity.
This research engineers T cells to target and eliminate specific B cells in order to treat autoimmune disease.

The immune system can be trained to attack itself to reverse a devastating autoimmune disease, in animal studies.
BBC News.
1 July 2016
http://www.bbc.co.uk/news/health-36662305

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease
Ellebrecht CT, Bhoj VG, Nace A, Jung Choi E, Mao X, Cho MJ, Di Zenzo G, Lanzavecchia A, Seykora JT, Cotsarelis G, Milone MC, Payne AS.
Science
Published Online 30 Jun 2016
http://science.sciencemag.org/content/early/2016/06/29/science.aaf6756
Abstract
Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Experimental research seeking a way to treat autoimmune disease without disrupting normal immune activity.
This research engineers T cells to target and eliminate specific B cells in order to treat autoimmune disease.

The immune system can be trained to attack itself to reverse a devastating autoimmune disease, in animal studies.
BBC News.
1 July 2016
http://www.bbc.co.uk/news/health-36662305

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease
Ellebrecht CT, Bhoj VG, Nace A, Jung Choi E, Mao X, Cho MJ, Di Zenzo G, Lanzavecchia A, Seykora JT, Cotsarelis G, Milone MC, Payne AS.
Science
Published Online 30 Jun 2016
http://science.sciencemag.org/content/early/2016/06/29/science.aaf6756

It is gratifying to see this development - which is the next step predicted to be the way to go after rituximab was shown to work. For eighteen years we have had little prospect of specific targeting but this makes sense as a possible way forward. It is likely to be much more difficult for abundant auto antigens like IgG Fc and DNA but the principle should still be viable. There remains the problem of clearing out plasma cells but that may be much less of an issue if auto reactive B cells can be targeted specifically.

At the moment i do not seem to be able to access the full text through UCL but will keep trying.
 

Keela Too

Sally Burch
Messages
900
Location
N.Ireland
That sounds interesting, and more refined than the way rituximab works.

The genetic engineering bit sounds a bit scary to me, but I guess there'd be loads of animal trials along the way.