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Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias
Feng Li1, Yuxing Hu2, Yan Wang1
1State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China.
Researchers developed a novel ferritin aggregation cell engager (FACE) to enhance chimeric antigen receptor T (CAR T) cell therapy for leukemia. This approach improves CAR T cell efficacy against antigen modulation and offers potential for combination therapy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimeric antigen receptor T (CAR T) cell therapy shows promise for leukemia treatment.
- Antigen modulation in leukemia cells leads to CAR T cell therapy resistance.
- CD71, a ferritin receptor, is co-expressed on leukemia cells and CAR T cells.
Purpose of the Study:
- To engineer a ferritin aggregation cell engager (FACE) to improve CAR T cell therapy efficacy.
- To overcome antigen modulation and enhance CAR T cell recognition of leukemia cells.
- To explore FACE-CAR T cells for combination therapy with chemodrugs.
Main Methods:
- Design and construction of FACE to anchor on CAR T cells.
- In vitro and in vivo testing using leukemia patient-derived cells and xenograft models.
- Evaluation of therapeutic efficacy, biosafety, and antigen modulation resistance.
Main Results:
- FACE-CAR T cells demonstrated enhanced therapeutic efficacy with good biosafety.
- The engineered CAR T cells lowered the antigen threshold, overcoming modulation.
- Potential for loading chemodrugs within ferritin for combination therapy was shown.
Conclusions:
- Avidity engineering with FACE provides a versatile approach to enhance CAR T cell therapy.
- This method improves efficacy for diverse refractory leukemias.
- FACE-CAR T cells represent a novel strategy for overcoming treatment resistance in leukemia.
