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Cytotoxic T-Lymphocyte-Associated Antigen 4 Antibody-Induced Colitis and Its Management with Infliximab

  • R. L. Johnston
  • J. Lutzky
  • A. Chodhry
  • J. S. BarkinEmail author
Case Report

Abstract

Anti-CTLA-4 antibodies are human monoclonal antibodies previously studied in the treatment of metastatic melanoma (MM). CTLA-4 is an inhibitory receptor on cytotoxic T cells, blockade of which will activate T cells allowing them to attack malignant cells. Normal host cells may also be affected, and immune-mediated enterocolitis can occur. This is a prospective observational study on the use of corticosteroids and infliximab in the treatment of patients with immune-mediated colitis secondary to anti-CTLA-4 antibody treatment of MM. Five patients presented with colitis after medication administration. Patients were treated with high-dose corticosteroids for 1 week, but diarrhea did not completely abate in any of them. They were then treated successfully with infliximab. One patient had recurrence of symptoms and responded to repeat treatment with infliximab. Patients who develop immune-mediated colitis after administration of anti-CTLA-4 antibodies have previously been reported to respond to corticosteroids, but in our study, all required treatment with infliximab.

Keywords

Colitis Antibodies Drug therapy Tremelimumab Infliximab T-Lymphocytes Immunology 

References

  1. 1.
    Beck KE, Blansfield JA, Tran KQ, et al. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol. 2006;24:2283–2289. doi: 10.1200/JCO.2005.04.5716.CrossRefPubMedGoogle Scholar
  2. 2.
    Reuben JM, Lee BN, Li C, et al. Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in patients with advanced malignant melanoma. Cancer. 2006;106:2437–2444. doi: 10.1002/cncr.21854.CrossRefPubMedGoogle Scholar
  3. 3.
    Pfizer announces discontinuation of phase III clinical trial for patients with advanced melanoma. Business Wire. 2008.Google Scholar
  4. 4.
    Medarex, Bristol-Myers delay BLA submission for ipilimumab; FDA seeks more data. Thomson Financial News. 2008.Google Scholar
  5. 5.
    Walunas TL, Lenschow DJ, Bakker CY, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1:405–413. doi: 10.1016/1074-7613(94)90071-X.CrossRefPubMedGoogle Scholar
  6. 6.
    Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182:459–465. doi: 10.1084/jem.182.2.459.CrossRefPubMedGoogle Scholar
  7. 7.
    Krummel MF, Allison JP. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med. 1996;183:2533–2540. doi: 10.1084/jem.183.6.2533.CrossRefPubMedGoogle Scholar
  8. 8.
    Chambers CA, Krummel MF, Boitel B, et al. The role of CTLA-4 in the regulation and initiation of T-cell responses. Immunol Rev. 1996;153:27–46. doi: 10.1111/j.1600-065X.1996.tb00919.x.CrossRefPubMedGoogle Scholar
  9. 9.
    Hodi FS, Mihm MC, Soiffer RJ, et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA. 2003;100:4712–4717. doi: 10.1073/pnas.0830997100.CrossRefPubMedGoogle Scholar
  10. 10.
    Phan GQ, Yang JC, Sherry RM, et al. Cancer regression and autoimmunity induced by CTLA-4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA. 2003;100:8372–8377. doi: 10.1073/pnas.1533209100.CrossRefPubMedGoogle Scholar
  11. 11.
    Sanderson K, Scotland R, Lee P, et al. Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and montanide ISA 51 for patients with resected stages III and IV melanoma. J Clin Oncol. 2005;23:741–750. doi: 10.1200/JCO.2005.01.128.CrossRefPubMedGoogle Scholar
  12. 12.
    Keler T, Halk E, Vitale L, et al. Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques. J Immunol. 2003;171:6251–6259.PubMedGoogle Scholar
  13. 13.
    Attia P, Phan GQ, Maker AV, et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anticytotoxic T-lymphocyte antigen-4. J Clin Oncol. 2005;23:6043–6053. doi: 10.1200/JCO.2005.06.205.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • R. L. Johnston
    • 1
    • 2
  • J. Lutzky
    • 3
  • A. Chodhry
    • 3
  • J. S. Barkin
    • 1
    • 2
    Email author
  1. 1.Division of GastroenterologyUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.Division of GastroenterologyMount Sinai Medical CenterMiami BeachUSA
  3. 3.Division of OncologyMount Sinai Medical CenterMiamiUSA

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