Self-Assembled Multivalent Aptamer Nanoparticles with Potential CAR-like Characteristics Could Activate T Cells and...

Area of Science:

• Biotechnology
• Immunotherapy
• Nanomedicine

Background:

• Chimeric antigen receptor (CAR)-T cell therapy shows promise but faces challenges in safety and efficacy.
• Aptamer-based nanostructures offer a versatile platform for targeted drug delivery and therapeutic applications.

Purpose of the Study:

• To develop and evaluate CAR-like multivalent aptamer nanoparticles (X-polymers) for enhanced T cell immunotherapy and melanoma treatment.
• To investigate the targeting capabilities and therapeutic effects of X-polymers in vitro and in vivo.

Main Methods:

• Assembly of X-polymers using CD28 and CTLA-4 RNA aptamers, and folic acid-labeled ssDNA in a nucleic acid scaffold.
• Confocal imaging and flow cytometry to assess cellular targeting of T cells and B16 melanoma cells.
• In vitro assays to evaluate T cell proliferation, IL-2 secretion inhibition, and B16 cell growth inhibition.
• In vivo studies to assess the anti-tumor efficacy of X-polymers against mouse melanoma.

Main Results:

• X-polymers successfully recognized and targeted both murine CD28 and CTLA-4 molecules on T cells and B16 cells.
• In vitro, X-polymers enhanced T cell proliferation and reversed IL-2 inhibition, while also inhibiting B16 cell growth.
• In vivo, X-polymers demonstrated significant inhibition of mouse melanoma B16 cell growth.

Conclusions:

• Multivalent aptamer nanoparticle-activated T cells can function similarly to CAR-T cells, representing a novel therapeutic strategy.
• This approach provides a multi-functional design for aptamer drugs with CAR-like characteristics, potentially enhancing the safety of CAR-T cell immunotherapy.