Biomimetic universal CAR-mesenchymal stem cell nanohybrids for anti-tumor therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunotherapy
• Oncology

Background:

• Current autologous CAR-T cell therapies face challenges like limited availability and long manufacturing times.
• Mesenchymal stem cells (MSCs) possess intrinsic tumor-homing capabilities.
• C-type lectin-like molecule-1 (CLL-1) is a specific marker on acute myeloid leukemia (AML) cells and leukemia stem cells (LSCs).

Purpose of the Study:

• To develop a universal CAR nanoplatform for improved AML therapy.
• To engineer MSCs with CAR and integrate them with multifunctional hybrid nanoparticles.
• To synergize chemotherapy and immunotherapy by targeting CLL-1.

Main Methods:

• Engineered mesenchymal stem cells (MSCs) with chimeric antigen receptor (CAR) targeting CLL-1 (aCLL-1 CAR-MSC).
• Integrated CAR-MSCs with multifunctional hybrid nanoparticles for targeted delivery of shikonin (SK) nanohybrids.
• Utilized biomimetic nanotechnology for enhanced drug delivery and immunogenic cell death induction.

Main Results:

• The nanoplatform demonstrated precise tumor targeting and eradication in AML models.
• Achieved 92.7% tumor inhibition rate and enhanced immune responses.
• Extended in vivo circulation time and induced M1 macrophage polarization.

Conclusions:

• This is the first nanoplatform to synergize chemotherapy and immunotherapy targeting CLL-1 for AML.
• The developed aCLL-1 CAR-MSC nanoplatform shows significant potential for AML treatment.
• Offers a robust foundation for clinical translation in AML and other malignancies.