Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease

Yonglian Sun, Helen M. Chen, Sumit K. Subudhi, Jonathan Chen, Rima Koka, Lieping Chen, Yang Xin Fu

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Humans and mice deficient in Fas, a tumor necrosis factor (TNF)-receptor family member, cannot induce apoptosis of autoreactive cells, and consequently develop progressive lymphoproliferative disorders and lupus-like autoimmune diseases. Previous studies have shown that short-term administrations of agonistic monoclonal antibodies against CD137, another TNF-receptor family member, activate T cells and induce rejection of allografts and established tumors. Here we report that treatment with an agonistic monoclonal antibody to CD137 (2A) blocks lymphadenopathy and spontaneous autoimmune diseases in Fas-deficient MRL/lpr mice, ultimately leading to their prolonged survival. Notably, 2A treatment rapidly augments IFN-γ production, and induces the depletion of autoreactive B cells and abnormal double-negative T cells, possibly by increasing their apoptosis through Fas- and TNF receptor-independent mechanisms. This study demonstrates that agonistic monoclonal antibodies specific for costimulatory molecules can be used as novel therapeutic agents to delete autoreactive lymphocytes and block autoimmune disease progression.

Original languageEnglish (US)
Pages (from-to)1405-1413
Number of pages9
JournalNature Medicine
Volume8
Issue number12
DOIs
StatePublished - Dec 1 2002

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Tumor Necrosis Factor Receptors
Autoimmune Diseases
T-cells
Monoclonal Antibodies
Molecules
Antibodies
Inbred MRL lpr Mouse
Apoptosis
T-Lymphocytes
Lymphoproliferative Disorders
Lymphocytes
Allografts
Disease Progression
Tumors
B-Lymphocytes
Therapeutics
Cells
Survival
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sun, Y., Chen, H. M., Subudhi, S. K., Chen, J., Koka, R., Chen, L., & Fu, Y. X. (2002). Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. Nature Medicine, 8(12), 1405-1413. https://doi.org/10.1038/nm796

Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. / Sun, Yonglian; Chen, Helen M.; Subudhi, Sumit K.; Chen, Jonathan; Koka, Rima; Chen, Lieping; Fu, Yang Xin.

In: Nature Medicine, Vol. 8, No. 12, 01.12.2002, p. 1405-1413.

Research output: Contribution to journalArticle

Sun, Y, Chen, HM, Subudhi, SK, Chen, J, Koka, R, Chen, L & Fu, YX 2002, 'Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease', Nature Medicine, vol. 8, no. 12, pp. 1405-1413. https://doi.org/10.1038/nm796
Sun Y, Chen HM, Subudhi SK, Chen J, Koka R, Chen L et al. Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. Nature Medicine. 2002 Dec 1;8(12):1405-1413. https://doi.org/10.1038/nm796
Sun, Yonglian ; Chen, Helen M. ; Subudhi, Sumit K. ; Chen, Jonathan ; Koka, Rima ; Chen, Lieping ; Fu, Yang Xin. / Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. In: Nature Medicine. 2002 ; Vol. 8, No. 12. pp. 1405-1413.
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