Dataset Information

Cross-Reactivity and Functionality of Approved Human Immune Checkpoint Blockers in Dogs.

ABSTRACT:

Background

Rodent cancer models have limitations in predicting efficacy, tolerability and accompanying biomarkers of ICIs in humans. Companion dogs suffering from neoplastic diseases have gained attention as a highly relevant translational disease model. Despite successful reports of PD-1/PD-L1 blockade in dogs, no compounds are available for veterinary medicine.

Methods

Here, we assessed suitability of seven FDA-approved human ICIs to target CTLA-4 or PD-1/PD-L1 in dogs. Cross-reactivity and blocking potential was assessed using ELISA and flow cytometry. Functional responses were assessed on peripheral blood mononuclear cells (PBMCs) derived from healthy donors (n = 12) and cancer patient dogs (n = 27) as cytokine production after stimulation. Immune composition and target expression of healthy donors and cancer patients was assessed via flow cytometry.

Results

Four candidates showed cross-reactivity and two blocked the interaction of canine PD-1 and PD-L1. Of those, only atezolizumab significantly increased cytokine production of healthy and patient derived PBMCs in vitro. Especially lymphoma patient PBMCs responded with increased cytokine production. In other types of cancer, response to atezolizumab appeared to correlate with a lower frequency of CD8 T cells.

Conclusions

Cross-functionality of atezolizumab encourages reverse translational efforts using (combination) immunotherapies in companion dog tumor patients to benefit both veterinary and human medicine.

SUBMITTER: Pantelyushin S

PROVIDER: S-EPMC7918463 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Cross-Reactivity and Functionality of Approved Human Immune Checkpoint Blockers in Dogs.

Pantelyushin Stanislav S Ranninger Elisabeth E Guerrera Diego D Hutter Gregor G Maake Caroline C Markkanen Enni E Bettschart-Wolfensberger Regula R Rohrer Bley Carla C Läubli Heinz H Vom Berg Johannes J

Cancers 20210213 4

<h4>Background</h4>Rodent cancer models have limitations in predicting efficacy, tolerability and accompanying biomarkers of ICIs in humans. Companion dogs suffering from neoplastic diseases have gained attention as a highly relevant translational disease model. Despite successful reports of PD-1/PD-L1 blockade in dogs, no compounds are available for veterinary medicine.<h4>Methods</h4>Here, we assessed suitability of seven FDA-approved human ICIs to target CTLA-4 or PD-1/PD-L1 in dogs. Cross-re ...[more]

PMID: 33668625

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Dataset Information

Cross-Reactivity and Functionality of Approved Human Immune Checkpoint Blockers in Dogs.

Background

Methods

Results

Conclusions

Publications

Cross-Reactivity and Functionality of Approved Human Immune Checkpoint Blockers in Dogs.

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