Immune Cell Modulation of Patient-Matched Organoid Drug Response in Precision Cancer Medicine Platform

Area of Science:

• Oncology
• Immunology
• Precision Medicine

Background:

• Cancer metastasis is a leading cause of cancer-related mortality.
• Precision cancer medicine (PCM) utilizes molecular alterations for targeted therapies.
• The tumor immune microenvironment's role in therapy response is often overlooked in current PCM platforms.

Purpose of the Study:

• To develop and evaluate a patient-matched organoid and immune cell co-culture system for drug testing.
• To investigate the impact of patient immune cells on treatment response within a co-culture PCM framework.
• To assess the efficacy of novel treatment strategies, including T-cell bispecific antibody testing.

Main Methods:

• Established patient-matched organoids and immune cell cultures.
• Utilized mono- and co-culture treatment setups with three distinct strategies.
• Evaluated treatment response and immune cell impact via tumor cell viability assays and flow cytometry.

Main Results:

• Phenotypic analysis revealed significant heterogeneity in tumor-infiltrating lymphocytes (TILs) and low immune cell content in organoids.
• Co-culture of patient immune cells with organoids demonstrated an impact on drug response and T-cell bispecific antibody efficacy in vitro.
• The developed pipeline successfully replicated patient treatment responses at the time of biopsy.

Conclusions:

• A patient-matched co-culture PCM approach is necessary to account for immune cell influence.
• Integrating immune cells into PCM organoid models enhances prediction of therapeutic outcomes.
• This co-culture pipeline represents a state-of-the-art method for personalized cancer therapy.