Format

Send to

Choose Destination
Int J Cancer. 2018 Sep 24. doi: 10.1002/ijc.31661. [Epub ahead of print]

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

Author information

1
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.
2
Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
3
Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD.
4
Department of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD.
5
Bristol-Myers Squibb Company, New York, NY.
6
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY.
7
Division Pediatric Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD.

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.

KEYWORDS:

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

PMID:
30248181
DOI:
10.1002/ijc.31661

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center