A 3D tumor spheroid model with robust T cell infiltration for evaluating immune cell engagers

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• The tumor microenvironment (TME) is crucial for cancer progression and response to therapy.
• Traditional 2D cell cultures do not fully represent the complex TME.
• Patient-derived xenografts (PDXs) offer a more relevant model but can be challenging to use for drug screening.

Purpose of the Study:

• To develop and validate a 3D tumor spheroid model from non-small cell lung cancer (NSCLC) PDX material.
• To enable T cell infiltration into the spheroids for studying immune responses.
• To establish a scalable platform for evaluating the efficacy of immunotherapeutic agents.

Main Methods:

• Generation of 3D tumor spheroids from NSCLC PDX tissues.
• Histologic and transcriptomic analysis to compare spheroids with original PDX tumors.
• Magnetic nanoparticle technology to facilitate T cell infiltration into spheroids.
• Assessment of T cell function, tumor-killing activity, and drug responses (viability, cytokine secretion).

Main Results:

• 3D tumor spheroids accurately recapitulated the histologic and transcriptomic features of the source PDX tumors.
• Consistent and functional T cell infiltration was achieved in the spheroids.
• The model demonstrated scalability for drug treatment studies, showing potential in evaluating immunotherapy agents.
• T cell function and anti-tumor activity were maintained within the 3D spheroid system.

Conclusions:

• The developed 3D tumor-T cell spheroid model is a valuable tool for studying the TME in NSCLC.
• This platform can effectively assess drug candidates targeting both tumor-intrinsic factors and the TME.
• The model holds potential for predicting patient responses to cancer therapies.
• It offers a more physiologically relevant system for preclinical drug evaluation compared to 2D models.