Mucin-1-Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in
Ru Zhou1, Shu-Ta Wu1,2, Mahboubeh Yazdanifar1,3
1Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC.
Abstract:
The chimeric antigen receptor (CAR) T-cell therapy in solid epithelial tumors has been explored, however, with limited success. As much of the preclinical work has relied on xenograft models in immunocompromised animals, the immune-related efficacies and toxicities may have been missed. In this study, we engineered syngeneic murine CAR T cells targeting the tumor form of human mucin-1 (tMUC1) and tested the MUC1 CAR T cells' efficacy and toxicity in the immunocompetent human MUC1-expressing mouse models. The MUC1 CAR T cells significantly eliminated murine pancreatic and breast cancer cell lines in vitro. In vivo, MUC1 CAR T cells significantly slowed the mammary gland tumor progression in the spontaneous PyVMT×MUC1.Tg (MMT) mice, prevented lung metastasis, and prolonged survival. Most importantly, there was minimal short or long-term toxicity with acceptable levels of transient liver toxicity but no kidney toxicity. In addition, the mice did not show any signs of weight loss or other behavioral changes with the treatment. We also report that a single dose of MUC1 CAR T-cell treatment modestly reduced the pancreatic tumor burden in a syngeneic orthotopic model of pancreatic ductal adenocarcinoma given at late stage of an established tumor. Taken together, these findings suggested the further development of tMUC1-targeted CAR T cells as an effective and relatively safe treatment modality for various tMUC1-expressing solid tumors.
Insights
Engineered chimeric antigen receptor (CAR) T cells targeting tumor mucin-1 (tMUC1) effectively reduced solid tumors in mice. This CAR T-cell therapy showed promising efficacy with minimal toxicity, suggesting potential for treating tMUC1-expressing cancers.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimeric antigen receptor (CAR) T-cell therapy shows limited success in solid epithelial tumors.
- Preclinical studies often use immunocompromised models, potentially missing immune-related efficacies and toxicities.
Purpose of the Study:
- To engineer and test syngeneic murine CAR T cells targeting the tumor form of human mucin-1 (tMUC1).
- To evaluate the efficacy and toxicity of MUC1 CAR T cells in immunocompetent mouse models expressing human MUC1.
Main Methods:
- Engineered syngeneic murine CAR T cells targeting tMUC1.
- Tested MUC1 CAR T cells in immunocompetent mouse models (PyVMT×MUC1.Tg and orthotopic pancreatic cancer models).
- Assessed in vitro cancer cell line elimination and in vivo tumor progression, metastasis, survival, and toxicity.
Main Results:
- MUC1 CAR T cells effectively eliminated murine pancreatic and breast cancer cell lines in vitro.
- In vivo, MUC1 CAR T cells slowed mammary tumor progression, prevented lung metastasis, and prolonged survival in MMT mice.
- Treatment resulted in minimal short/long-term toxicity, including transient liver effects but no kidney toxicity, and no significant weight loss or behavioral changes.
Conclusions:
- tMUC1-targeted CAR T cells demonstrate significant efficacy against solid tumors in immunocompetent models.
- The therapy is relatively safe, with manageable side effects.
- These findings support the further development of tMUC1 CAR T cells for treating various solid tumors.
More Related Videos
08:46A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
09:56A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
Related Concept Videos
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...