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Expression of LAG‐3 and efficacy of combination treatment with anti‐LAG‐3 and anti‐PD‐1 monoclonal antibodies in glioblastoma
Author(s) -
HarrisBookman Sarah,
Mathios Dimitrios,
Martin Allison M.,
Xia Yuanxuan,
Kim Eileen,
Xu Haiying,
Belcaid Zineb,
Polanczyk Magdalena,
Barberi Theresa,
Theodros Debebe,
Kim Jennifer,
Taube Janis M.,
Burger Peter C.,
Selby Mark,
Taitt Corina,
Korman Alan,
Ye Xiaobu,
Drake Charles G.,
Brem Henry,
Pardoll Drew M.,
Lim Michael
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31661
Subject(s) - glioblastoma , monoclonal antibody , immunotherapy , antibody , immune system , immune checkpoint , lag , cancer research , lag time , glioma , medicine , immunology , biology , computer science , computer network , biological system
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.