Targeted theranostic nanomedicine using targeted CT-imageable particles that release tebentafusp

Area of Science:

• Nanomedicine
• Immunotherapy
• Radiotherapy

Background:

• Targeting CD3+ bispecific antibodies is crucial for effective cancer immunotherapy.
• Developing theranostic agents offers dual diagnostic and therapeutic benefits.
• Hyaluronate-alginate nanoparticles show potential for targeted drug delivery and release upon radiation exposure.

Purpose of the Study:

• To evaluate a novel theranostic nanomedicine for CD3+ bispecific antibodies targeting glycoprotein-100 (GP-100) in vivo.
• To assess the efficacy of radiation-triggered release of therapeutic agents from CT-imageable nanoparticles.
• To investigate the synergistic effects of this nanomedicine combined with radiation therapy in a B16-melanoma mouse model.

Main Methods:

• Development of hyaluronate-alginate nanoparticles encapsulating IFN-γ and tebentafusp.
• Intravenous injection of nanoparticles followed by two sessions of targeted X-ray radiation (10 or 20 Gy).
• In vivo evaluation in a mouse model with primary B16-melanoma and pulmonary metastases, utilizing CT imaging for visualization.

Main Results:

• IFN-γ nanoparticles selectively accumulated in tumors and metastases, visualized by CT.
• Nanoparticle-released IFN-γ and tebentafusp facilitated immune synapse formation and T cell-mediated tumor cell lysis.
• Combined therapy demonstrated synergistic effects with an Enhancement Factor (EF) greater than 1, indicating enhanced tumor destruction.

Conclusions:

• The theranostic nanomedicine shows promise as a dual therapeutic and diagnostic tool.
• The combination of nanomedicine and radiation therapy offers a synergistic approach for treating primary tumors and metastases.
• This strategy holds potential for improved cancer treatment outcomes.