Combination therapy with anti-CTL antigen-4 and anti-4-1BB antibodies enhances cancer immunity and reduces autoimmunity

Ergun Kocak, Kenneth Lute, Xing Chang, Kenneth F. May, Katie R. Exten, Huiming Zhang, Shahab F. Abdessalam, Amy M. Lehman, David Jarjoura, Pan Zheng, Yang Liu

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121 Scopus citations

Abstract

The majority of cancer antigens identified thus far have limited expression in normal tissues. It has been suggested that autoimmune disease is a necessary price for cancer immunity. This notion is supported by a recent clinical trial involving an anti-CTL antigen-4 (CTLA-4) antibody that showed significant clinical responses but severe autoimmune diseases in melanoma patients. To selectively modulate cancer immunity and autoimmunity, we used anti-CTLA-4 and anti-4-1BB antibodies to treat mice with a preexisting cancer, MC38. The combination of the two antibodies led to CD8 T-cell-mediated rejection of large established MC38 tumors and long-lasting immunity to the same tumor cells, although the same regimen was not effective for B16 melanoma. More importantly, whereas individual antibodies induced inflammation and autoimmune manifestations, combination therapy increased cancer immunity while reducing autoimmunity. The reduction of autoimmune effects correlates with an increased function of regulatory T cells. Our results suggest a novel approach to simultaneously enhance cancer immunity and reduce autoimmunity.

Original languageEnglish (US)
Pages (from-to)7276-7284
Number of pages9
JournalCancer Research
Volume66
Issue number14
DOIs
StatePublished - Jul 15 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kocak, E., Lute, K., Chang, X., May, K. F., Exten, K. R., Zhang, H., Abdessalam, S. F., Lehman, A. M., Jarjoura, D., Zheng, P., & Liu, Y. (2006). Combination therapy with anti-CTL antigen-4 and anti-4-1BB antibodies enhances cancer immunity and reduces autoimmunity. Cancer Research, 66(14), 7276-7284. https://doi.org/10.1158/0008-5472.CAN-05-2128