In-depth cross-validation of human and mouse CD4-specific minibodies for noninvasive PET imaging of CD4+ cells and response prediction to cancer immunotherapy

Pezzana S
August 1, 2024
Theranostics
https://pubmed.ncbi.nlm.nih.gov/39239511/

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/39239511/

Research summary

This study compares human and mouse CD4-targeting minibodies for PET imaging of CD4⁺ T cells. Using the humanized hCD4 Knockin mouse model, researchers demonstrated that a human CD4-specific minibody provides high-contrast, specific imaging of CD4⁺ T cells and can be used to monitor and predict response to immunotherapy. The model allowed precise in vivo evaluation of tracer specificity and translational potential for human use.

Key outcome of the study

The human CD4 minibody demonstrated specific binding and imaging in vivo, and PET imaging using this tracer enabled prediction of cancer immunotherapy response, supporting its use as a noninvasive biomarker tool.

Mouse model

Humanized CD4 (hCD4) Knockin mouse model developed by genOway, with the extracellular domain of human CD4 replacing the murine counterpart, enabling evaluation of human-targeted tracers.

TARGET:
CD4
T4 antigen, Leu-3, L3T4

Keywords

CD4⁺ T cell tracking, Cancer immunotherapy, PET imaging, Noninvasive biomarker, Immunomonitoring

Technical specifications

Humanized Knockin model, CD4 extracellular domain replacement, ImmunoPET, Tracer validation, Biomarker development

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The humanized genO‑hCD4 mouse model allows in vivo efficacy and safety assessment of anti-human CD4 compounds.

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