Expression of LAG-3 and efficacy of combination treatment with anti-LAG-3 and anti-PD-1 monoclonal antibodies in glioblastoma

Sarah Harris-Bookman, Dimitrios Mathios, Allison M. Martin, Yuanxuan Xia, Eileen Kim, Haiying Xu, Zineb Belcaid, Magdalena Polanczyk, Theresa Barberi, Debebe Theodros, Jennifer Kim, Janis M. Taube, Peter C. Burger, Mark Selby, Corina Taitt, Alan Korman, Xiaobu Ye, Charles G. Drake, Henry Brem, Drew M. PardollMichael Lim

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Like in many tumor types, immunotherapy is currently under investigation to assess its potential efficacy in glioblastoma patients. Trials are under way to assess the efficacy of new immune checkpoint inhibitors including anti-PD-1 or CTLA4. We here investigate the expression and efficacy of a novel immune-checkpoint inhibitor, called LAG-3. We show that LAG-3 is expressed in human glioblastoma samples and in a mouse glioblastoma model we show that knock out or LAG-3 inhibition with a blocking antibody is efficacious against glioblastoma and can be used in combination with other immune checkpoint inhibitors toward complete eradication of the model glioblastoma tumors. From a mechanistic standpoint we show that LAG-3 expression is an early marker of T cell exhaustion and therefore early treatment with LAG-3 blocking antibody is more efficacious than later treatment. These data provide insight and support the design of trials that incorporate LAG-3 in the treatment of glioblastoma.

Original languageEnglish (US)
Pages (from-to)3201-3208
Number of pages8
JournalInternational Journal of Cancer
Volume143
Issue number12
DOIs
StatePublished - Dec 15 2018
Externally publishedYes

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Keywords

  • anti-LAG-3
  • anti-PD-1
  • glioblastoma
  • IFN-γ
  • T cell exhaustion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Harris-Bookman, S., Mathios, D., Martin, A. M., Xia, Y., Kim, E., Xu, H., Belcaid, Z., Polanczyk, M., Barberi, T., Theodros, D., Kim, J., Taube, J. M., Burger, P. C., Selby, M., Taitt, C., Korman, A., Ye, X., Drake, C. G., Brem, H., ... Lim, M. (2018). Expression of LAG-3 and efficacy of combination treatment with anti-LAG-3 and anti-PD-1 monoclonal antibodies in glioblastoma. International Journal of Cancer, 143(12), 3201-3208. https://doi.org/10.1002/ijc.31661