Anti-PSMA/CD3 Bispecific Antibody Delivery and Antitumor Activity Using a Polymeric Depot Formulation

Wilhem Leconet1, He Liu2, Ming Guo2

  • 1Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, New York. wil2011@med.cornell.edu.

Insights

A novel injectable polymer system successfully delivered BiJ591, a bispecific T-cell engager, for sustained prostate cancer treatment. This controlled release enhanced therapeutic efficacy compared to daily injections.

Area of Science:

  • Oncology
  • Biomaterials Science
  • Drug Delivery Systems

Background:

  • Small therapeutic proteins offer promise for cancer treatment but face challenges due to short plasma half-life and limited stability.
  • Controlled long-term delivery of hydrophilic and potentially unstable biologicals remains a significant hurdle in clinical applications.

Purpose of the Study:

  • To develop and evaluate an in situ forming, injectable polymeric depot system for the controlled delivery of BiJ591, a bispecific T-cell engager (BiTE).
  • To assess the stability, release kinetics, and therapeutic efficacy of BiJ591 delivered via the polymeric system in prostate cancer models.

Main Methods:

  • Utilized diblock (DB) and triblock (TB) biodegradable polyethylene glycol-poly(lactic acid) (PEG-PLA) copolymers solubilized in tripropionin to create an injectable depot.
  • Administered the BiJ591-loaded polymeric formulation subcutaneously in mice with prostate cancer xenografts.
  • Evaluated BiJ591 release profiles, stability, T-cell activation, and tumor growth inhibition.

Main Results:

  • The triblock copolymer formulation (TB1/DB4) demonstrated sustained release of BiJ591 for up to 21 days after a single subcutaneous injection.
  • The BiJ591-TB1/DB4 formulation showed significant therapeutic activity in both low and high PSMA-expressing prostate cancer xenografts.
  • This controlled delivery approach was more effective than daily intravenous administration of BiJ591.

Conclusions:

  • Injectable PEG-PLA copolymer depots provide a viable strategy for the controlled, long-term delivery of small therapeutic proteins like BiJ591.
  • This formulation enhances the therapeutic efficacy of BiTEs in prostate cancer treatment, offering a promising alternative to conventional administration methods.

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