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Updated: Nov 12, 2025

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
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Oncolytic adeno-immunotherapy modulates the immune system enabling CAR T-cells to cure pancreatic tumors

Amanda Rosewell Shaw1,2, Caroline E Porter1,2, Tiffany Yip1,2

  • 1Department of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA.

Communications Biology
|March 20, 2021
PubMed

Insights

This study combines oncolytic immunotherapy (CAdTrio) with HER2-CAR T-cells to effectively treat pancreatic cancer (PDAC). The combination therapy demonstrated potent and durable tumor eradication in preclinical models.

Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Biology

Background:

  • High human epidermal growth factor receptor 2 (HER2) expression correlates with poor prognosis in pancreatic ductal adenocarcinoma (PDAC).
  • Previous HER2-targeting immunotherapies for PDAC have shown limited success.

Purpose of the Study:

  • To enhance the efficacy, potency, and duration of HER2-specific CAR T-cell (HER2.CART) therapy against PDAC.
  • To evaluate a novel combination strategy using CAdTrio oncolytic immunotherapy and HER2.CARTs for PDAC treatment.

Main Methods:

  • Developed CAdTrio, an oncolytic adeno-immunotherapy producing cytokines, immune checkpoint blockade, and a safety switch.
  • Tested the combination of CAdTrio and HER2.CARTs in PDAC xenograft and humanized mouse models.
  • Assessed modifications in the tumor immune microenvironment and systemic immune responses.

Main Results:

  • Combination treatment with CAdTrio and HER2.CARTs achieved complete tumor cure in PDAC xenograft models.
  • Durable tumor responses were observed in humanized mice.
  • Intratumoral CAdTrio promoted HER2.CART migration and stimulated systemic immune responses that enhanced anti-tumor activity in distant tumors.

Conclusions:

  • CAdTrio and HER2.CARTs exhibit complementary activities for eradicating metastatic PDAC.
  • This combination therapy holds promise as a co-operative treatment strategy for PDAC patients.

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