Poster 3809: IDO1 Inhibition Assay Measuring Kyn Levels Developed

T Cell Activation Through the Inhibition of Tumor-Expressed IDO1 Activity in the Tryptophan Metabolism Pathway

Chunlan Dong, Ying Wang, Kefeng Gong, Teng Lu, Frank Xing, and Qian Shi

IDO1 is a major mechanism of immunosuppression in tumors, with expression of IDO1 by tumor cells resulting in aggressive tumor growth and disease resistance to T cell-targeting immunotherapies.

To investigate the de-suppression of T cell function through inhibition of the IDO1-mediated tryptophan metabolism pathway, CrownBio has established an in vitro assay system which allows the robust LC-MS/MS detection of the levels of N-formyl-kynurenine (a tryptophan metabolism product) in culture medium, plasma, and tumor tissue.

This poster details initial investigations into IDO1 expression with and without IFN-γ induction, how IDO1 inhibition reduces the levels of kynurenine in culture medium, and the correlation of the reduction of kynurenine production with the re-activation of T cell activity.

Read this Poster to Discover:

• That, from cell lines screened, a selection of model tumor cell lines constitutively express IDO1, while half of the tumor cell lines tested express IDO1 in an IFN-γ-dependent manner, with the other half proving non-responsive to cytokine stimulation
• That longer compound treatment offers a more robust detection window for Kyn
• A co-culture system comprising of T cells and HeLa cells which can be used to correlate effective reduction of Kyn production to re-activation of T cell activity, in which T cell proliferation can be activated upon IDO1 inhibition

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