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Related Experiment Video

Updated: Oct 7, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

A Model-Based Framework to Identify Optimal Administration Protocols for Immunotherapies in Castration-Resistance

Roberta Coletti¹, Andrea Pugliese², Andrea Lunardi³

¹Fondazione The Microsoft Research, University of Trento Centre for Computational and Systems Biology (COSBI), 38068 Rovereto, Italy.

|January 11, 2022

Summary

This summary is machine-generated.

Mathematical modeling suggests high-dose, short-term ipilimumab (anti-CTLA4) is optimal for castration-resistant prostate cancer (CRPC). Combining ipilimumab with sipuleucel-T enhances tumor control and reduces ipilimumab dosage.

Keywords:

computational biology immunotherapy ipilimumab mathematical modeling optimal administration protocols optimization problems ordinary differential equations (ODEs)prostate cancer sipuleucel-T toxicity function

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Published on: October 24, 2019

Area of Science:

Oncology
Immunotherapy
Mathematical Modeling

Background:

Prostate cancer (PCa) frequently affects males, with castration-resistant prostate cancer (CRPC) becoming incurable.
CRPC exhibits resistance to immunotherapies, with only sipuleucel-T approved.
Anti-CTLA4 therapies are being investigated for CRPC treatment.

Purpose of the Study:

To determine optimal administration protocols for ipilimumab in CRPC.
To evaluate ipilimumab as a single treatment versus in combination with sipuleucel-T.
To consider both anti-tumor effects and drug toxicity in treatment optimization.

Main Methods:

Development of a mathematical model for CRPC.
Inclusion of a dose-dependent toxicity function derived from experimental data.
Definition and solving of two distinct optimization problems.

Main Results:

High-dose, short-duration ipilimumab administration is predicted to be more effective than prolonged low-dose regimens.
A synergistic effect was observed between ipilimumab and sipuleucel-T, improving tumor control.
Lower ipilimumab doses are feasible when combined with sipuleucel-T.

Conclusions:

Mathematical modeling provides insights into optimizing anti-CTLA4 therapy for CRPC.
Combination therapy with ipilimumab and sipuleucel-T shows promise for enhanced CRPC management.
Patient-specific factors may influence the potential for complete tumor eradication.