Arming Immune Cell Therapeutics with Polymeric Prodrugs

Area of Science:

• Immunology
• Biotechnology
• Pharmacology

Background:

• Engineered immune cells offer promising cancer treatment strategies.
• Current methods face challenges in drug delivery and overcoming tumor immune suppression.

Purpose of the Study:

• To develop a versatile platform for arming immune cells with therapeutic agents.
• To engineer macrophages and T cells for targeted drug delivery and transgene regulation.

Main Methods:

• Engineered macrophages and T cells to express a bioorthogonal single chain variable fragment receptor.
• Developed "drugamers" - polymeric prodrugs tagged with a fluorescein ligand for cell binding.
• Incorporated PI-103 prodrug monomers into drugamers for sustained drug release.
• Utilized a second drugamer with an estrogen analog (CMP8) for transgene regulation in T cells.

Main Results:

• Achieved stable binding of drugamers to engineered macrophages with 80% surface retention over 10 days.
• Demonstrated sustained antiproliferative activity against glioblastoma using PI-103 released from drugamers.
• Showcased the system's versatility by arming T cells with a transgene-regulating drugamer.

Conclusions:

• The developed bioorthogonal receptor and drugamer system effectively arms immune cells.
• This platform enables targeted delivery of both antitumor and transgene-activating small molecule prodrugs.
• The system offers a modular and versatile approach for advanced cell-based therapies.