AACR 2025 Poster 7270

Novel Humanized Cell and Murine Models Expressing Tumor Associated Antigens for ADC Toxicity and IO Combination Evaluation

Sylvia Xiaoze Wang, Lily Rong Wang, Kaixia Lian, Rongfei Lu, Jian Feng, Jun Zhou, Xiaolong Tu, Xinhe Feng, Jie Lin, Fuping Xu, Ludovic Bourre, Jessie JingJing Wang

Antibody-drug conjugates (ADCs) are transforming cancer therapy by combining targeted cytotoxicity with immune activation, offering potential synergy with PD-1 inhibitors. However, traditional mouse models lack functional immune systems or human antigen expression, limiting their predictive power.

To overcome these challenges, we developed humanized tumor models expressing tumor-associated antigens (hTAAs) and genetically modified mice with functional immune systems. These models enable comprehensive evaluation of ADC efficacy, pharmacokinetics, and toxicity in a clinically relevant setting.

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• Clinically Relevant ADC Testing: Humanized tumor and mouse models provide a more accurate preclinical system to evaluate ADC efficacy, immune response, and combination therapies.
  
  
• Pharmacokinetics & Toxicity Insights: These models improve the assessment of ADC half-life, biodistribution, and toxicity, reflecting clinical observations.
  
  
• Enhanced Combination Therapy Studies: Using PD-1 inhibitors with ADCs demonstrated significant tumor growth inhibition and complete response rates in humanized models.

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