opportunistic autoimmune disorders potentiated by immune-checkpoint inhibitors anti-ctla-4 and anti-pd-1
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2014
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Abstract
To improve the efficacy of immunotherapy for cancer and autoimmune diseases, recent ongoing and completed clinical trials have focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process. In a previous review (Kong et al., Ann. N.Y. Acad. Sci. 1183:222-236, 2010), both systemic immunomodulators and monoclonal antibodies, anti-CTLA-4 and anti-CD52, were discussed regarding therapeutics and autoimmune sequelae, as well as predisposing factors known to exacerbate immune-related adverse events. This review will focus on immune-checkpoint inhibitors, and the data from most clinical trials involve blockade with anti-CTLA-4 such as ipilimumab. However, despite the mild to severe immune-related adverse events observed with ipilimumab in ~60% of patients, overall survival averaged ~22-25% at 3-5 years. To boost overall survival, other monoclonal antibodies targeting programmed death-1 and its ligand are undergoing clinical trials as monotherapy or dual therapy with anti-CTLA-4. Therapeutic combinations may generate different spectrum of opportunistic autoimmune disorders. To simulate clinical scenarios, we have applied regulatory T cell perturbation to murine models combined to examine the balance between thyroid autoimmunity and tumor-specific immunity.
| Reference Key |
ekong2014frontiersopportunistic
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|---|---|
| Authors | ;Yi-Chi eKong;Jeffrey C. Flynn |
| Journal | sudebno-meditsinskaia ekspertiza |
| Year | 2014 |
| DOI |
10.3389/fimmu.2014.00206
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