Mini Review ARTICLE

Front. Immunol., 15 May 2014 | doi: 10.3389/fimmu.2014.00206

Opportunistic autoimmune disorders potentiated by immune-checkpoint inhibitors anti-CTLA-4 and anti-PD-1

imageYi-chi M. Kong1* and imageJeffrey C. Flynn2
  • 1Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA
  • 2Department of Orthopaedic Surgery, Providence Hospital and Medical Centers, Southfield, MI, USA

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, both systemic immunomodulators and monoclonal antibodies (mAbs), 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 (irAEs). 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 irAEs observed with ipilimumab in ~60% of patients, overall survival (OS) averaged ~22–25% at 3–5 years. To boost OS, other mAbs targeting programed 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.

Keywords: anti-CTLA-4, anti-PD-1, autoimmune disease, tumor immunity, immune-checkpoint inhibitor

Citation: Kong YM and Flynn JC (2014) Opportunistic autoimmune disorders potentiated by immune-checkpoint inhibitors anti-CTLA-4 and anti-PD-1. Front. Immunol. 5:206. doi: 10.3389/fimmu.2014.00206

Received: 11 February 2014; Accepted: 25 April 2014;
Published online: 16 May 2014.

Edited by:

Fang-Ping Huang, Imperial College London, UK

Reviewed by:

Christopher E. Rudd, University of Cambridge, UK
José Mordoh, Fundación Instituto Leloir, Argentina
Julian Pardo, Fundación Agencia Aragonesa para la Investigación y el Desarrollo, Spain

Copyright: © 2014 Kong and Flynn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Yi-chi M. Kong, Department of Immunology and Microbiology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201, USA e-mail: ykong@med.wayne.edu

Back to top