Treatment of pemphigus beyond rituximab: chimeric autoantibody receptor T cell (CAAR-T cell) therapy

Öz

Pemphigus vulgaris is a rare, life-threatening, autoimmune bullous disease. After decades of systemic corticosteroids and corticosteroid-sparing immunosuppressants being used to control the disease, the efficacy of rituximab has been shown in randomized controlled studies. Hence rituximab constitutes the first-line treatment for mild and moderate-to-severe pemphigus vulgaris according to the most recent European S2K guideline. Despite promising results with rituximab, there is still no disease-specific treatment available. In that regard, chimeric autoantibody receptor therapy (CAAR-T cell therapy) is under the spotlight utilizing a cutting-edge technology.

Anahtar Kelimeler

• CAAR-T cell therapy
• pemphigus
• chimeric autoantibody receptor therapy
• cellular immunotherapy

Proje Numarası

bulunmuyor

Pemfigus tedavisinde rituksimabın ötesi: Kimerik otoantikor reseptör T hücre (CAAR-T hücre) tedavisi

Öz

Pemfigus vulgaris, nadir görülen, hayatı tehdit eden bir otoimmün büllöz hastalıktır. Hastalığı kontrol etmek için uzun yıllar sistemik kortikosteroid ve adjuvan immünsüpresiflerin kullanılmasının ardından, randomize kontrollü çalışmalarla rituksimabın hastalıktaki etkinliği gösterildi. Böylece rituksimab en güncel Avrupa S2K kılavuzunda hafif ve orta-şiddetli pemfigus vulgarisin ilk sıra tedavi seçeneği olarak yerini aldı. Rituksimab ile her ne kadar umut verici yanıtlar elde edilse de, henüz hastalığa spesifik bir tedavi bulunmamaktadır. Bu bağlamda, en son teknoloji kullanılarak yapılan kimerik otoantikor reseptör tedavisi (CAAR-T hücre tedavisi) tüm ilgiyi üzerine toplamıştır.

Anahtar Kelimeler

• pemfigus
• kimerik otoantikor reseptör tedavisi
• hücresel immünoterapi
• CAAR-T hücre tedavisi

Destekleyen Kurum

bulunmuyor

Proje Numarası

bulunmuyor

Kaynakça

1. Joly P, Horvath B, Patsatsi A, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol 2020;34:1900-13.
2. Tavakolpour S, Mahmoudi H, Balighi K, Abedini R, Daneshpazhooh M. Sixteen-year history of rituximab therapy for 1085 pemphigus vulgaris patients: A systematic review. Int Immunopharmacol 2018;54:131-8.
3. Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial Lancet 2017;389:2031-40.
4. Musette P, Bouaziz JD. B cell modulation strategies in autoimmune diseases: new concepts. Front Immunol 2018;9:622.
5. Ellebrecht CT, Payne AS. Setting the target for pemphigus vulgaris therapy. JCI Insight 2017;2:e92021.
6. Aalberse RC, Schuurman J. IgG4 breaking the rules. Immunology 2002;105:9-19.
7. Futei Y, Amagai M, Ishii K, Kuroda-Kinoshita K, Ohya K, Nishikawa T. Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus. J Dermatol Sci 2001;26:55-61.
8. Funakoshi T, Lunardon L, Ellebrecht CT, Nagler AR, O’Leary CE, Payne AS. Enrichment of total serum IgG4 in patients with pemphigus. Br J Dermatol 2012;167:1245-53.

9. Edwards JC, Cambridge G. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 2006;6:394-403.
10. Eming R, Nagel A, Wolff-Franke S, Podstawa E, Debus D, Hertl M. Rituximab exerts a dual effect in pemphigus vulgaris. J Invest Dermatol 2008;128:2850-8.
11. Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med 2013;5:175ra30.
12. Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:613-20.
13. Hammers CM, Chen J, Lin C, et al. Persistence of anti-desmoglein 3 IgG(+) B-cell clones in pemphigus patients over years. J Invest Dermatol 2015;135:742-9.
14. Graves JE, Nunley K, Heffernan MP. Off-label uses of biologics in dermatology: rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept (part 2 of 2). J Am Acad Dermatol 2007;56:e55-79.
15. Haddadi MH, Hajizadeh-Saffar E, Khosravi-Maharlooei M, Basiri M, Negahdari B, Baharvand H. Autoimmunity as a target for chimeric immune receptor therapy: A new vision to therapeutic potential. Blood Rev 2020;41:100645.
16. Zhang Q, Lu W, Liang CL, et al. Chimeric antigen receptor (CAR) treg: a promising approach to inducing immunological tolerance. Front Immunol 2018;9:2359.
17. Fransson M, Piras E, Burman J, et al. CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery. J Neuroinflammation 2012;9:112.
18. MacDonald KG, Hoeppli RE, Huang Q, et al. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J Clin Invest 2016;126:1413-24.
19. Boardman DA, Philippeos C, Fruhwirth GO, et al. Expression of a chimeric antigen receptor specific for donor HLA class i enhances the potency of human regulatory T cells in preventing human skin transplant rejection. Am J Transplant 2017;17:931-43.
20. Salter AI, Pont MJ, Riddell SR. Chimeric antigen receptor-modified T cells: CD19 and the road beyond. Blood 2018;131:2621-9.
21. Simon B, Uslu U. CAR-T cell therapy in melanoma: a future success story? Exp Dermatol 2018;27:1315-21.
22. Flemming A. Autoimmune diseases: CAR-T cells take aim at autoimmunity. Nat Rev Drug Discov 2016;15:603.
23. Siddiqi HF, Staser KW, Nambudiri VE. Research techniques made simple: CAR T-Cell therapy. J Invest Dermatol 2018;138:2501-4.e1.
24. Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics 2016;3:16011.
25. Rubin CB, Elenitsas R, Taylor L, et al. Evaluating the skin in patients undergoing chimeric antigen receptor modified T-cell therapy. J Am Acad Dermatol 2016;75:1054-7.
26. Hege KM, Bergsland EK, Fisher GA, et al. Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer. J Immunother Cancer 2017;5:22.
27. Siegler E, Li S, Kim YJ, Wang P. Designed ankyrin repeat proteins as Her2 targeting domains in chimeric antigen receptor-engineered T cells. Hum Gene Ther 2017;28:726-36.
28. Han X, Cinay GE, Zhao Y, Guo Y, Zhang X, Wang P. Adnectin-based design of chimeric antigen receptor for T cell engineering. Mol Ther 2017;25:2466-76.
29. Grada Z, Hegde M, Byrd T, et al. TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids 2013;2:e105.
30. Cho JH, Collins JJ, Wong WW. Universal Chimeric antigen receptors for multiplexed and logical control of T cell responses. Cell 2018;173:1426-38.e11.
31. Atilla PA, Atilla E. Resistance against anti-CD19 and anti-BCMA CAR T cells: recent advances and coping strategies. Transl Oncol 2022;22:101459.
32. Wegner A. Chimeric antigen receptor T cells for the treatment of cancer and the future of preclinical models for predicting their toxicities. Immunotherapy 2017;9:669-80.
33. Ellebrecht CT, Bhoj VG, Nace A, et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science 2016;353:179-84.