SITC 2025 Poster #714

Humanized Engineered Syngeneic Mice Models for ADC/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 

Crown Bioscience introduces syngeneic and genetically engineered mouse models (GEMMs) designed to assess the synergy between antibody-drug conjugates and immune checkpoint inhibitors. This study highlights how these immune-competent models reveal antigen retention, immune activation, and durable responses, advancing the preclinical evaluation of ADC–IO combinations.

In this study, Crown Bioscience demonstrates the use of syngeneic and genetically engineered mouse models (GEMMs) to evaluate combination therapies involving antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs). These models maintain an intact immune system, providing a physiologically relevant environment to study therapeutic synergy, antigen dynamics, and immune modulation not achievable in traditional xenograft systems.

Download this Poster to Discover:

• Synergistic Efficacy of DS-8201 and Anti-PD-1 Therapy: Learn how combining Enhertu (DS-8201) with anti-PD-1 antibodies produced robust synergistic anti-tumor effects and complete responses in C57BL/6 and C57BL/6-hHer2 mice bearing MC38-hHer2 tumors.
  
  
• Advanced Syngeneic and GEMM Models: Explore how genetically engineered hHer2 mouse models exhibited superior antigen retention and tumor growth dynamics, supporting more predictive evaluation of HER2-targeted ADCs.
  
  
• Immune Profiling Insights: Discover how flow cytometry-based immune profiling revealed increases in T-cell infiltration, expansion of naïve and central memory CD8⁺ T cells, and reductions in exhausted CD8⁺ populations — key indicators of durable anti-tumor immunity.
  
  
• Evidence of Long-Term Immune Memory: Review re-challenge experiments showing sustained immune protection in responders, underscoring the potential of ADC and checkpoint blockade combinations to elicit lasting immunologic responses.
  
  
• Predictive Preclinical Platform for Combination Therapy: Utilize syngeneic and GEMM systems as translational models for testing ADC–IO combinations, dissecting mechanisms of action, and guiding rational combination strategies for clinical advancement.

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