Organ Model: Cancer Models

Heidelberg MPS Day, held on October 1st, 2024, was a one-day Organ-Chip User Group Meeting centered around the theme of “Disease-on-Chip: Insights from Cancer, Infectious Disease & Respiratory Models.”

At this event, Organ-Chip users and enthusiasts from across Europe came together to attend expert-led sessions, network, and discuss the latest advancements in the field.

Featured talks include:

“The Human Emulation System – Advancing Research in Cancer and Infectious Diseases” by Christine Lansche, PhD, Scientific Liaison, Emulate

“Alveolus Lung-Chip for Studying Alveolar Niche and Lung Repair” by Irina Shalashova, PhD, Postdoctoral Researcher, Boehringer Ingelheim

“Cord Formation and Alveolar Immunity – Harnessing Microphysiological Models to Study Humanity’s Oldest Foe” by Vivek Thacker, PhD, Group Leader, Heidelberg University Medical Faculty

“Cancer-Bone Crosstalk in an Organ-Chip Model of Breast Cancer Metastases” by Stefaan Verbruggen, PhD, Assistant Professor of Medical Technology, Queen Mary University of London

“Modelling Cancer-Microbe Interactions with Organoids and Organs-on-Chips” by Jens Puschhof, PhD, Principal Investigator, DKFZ

“Microbial Insights in Oncology” by Rafik Fellague-Chebra, MD, Msc, Executive Global Group Medical Director, Novartis

“Exacerbation of Influenza Virus Induced Lung Injury by Alveolar Macrophages and Its Suppresion by Pyroptosis Blockade in a Human Lung Alveolus Chip” by Yuncheng Man, PhD, Postdoctoral Research Fellow, Wyss Institute & Boston Children’s Hospital

Chimeric antigen receptor (CAR) T-cell therapy shows significant potential in treating various human cancers. Unfortunately, researchers have faced difficulty in adapting this therapy to target solid tumors, where CAR T cells face unique challenges, such as antigen heterogeneity, an immuno-suppressive microenvironment, and T-cell exhaustion.  

However, none of these challenges matter unless the CAR T cells can extravasate out of the blood stream and successfully migrate to the site of the tumor—an often-overlooked yet critical rate-limiting part of the process that cannot be modeled in conventional cell cultures. 

To address this, Emulate has recently launched a validated Organ-Chip workflow enabling researchers to model the entire journey of solid tumor CAR T-cell therapy in a vascularized cancer cell line model. 

In this data-driven webinar, Emulate Principal Scientist Anita Mehta, PhD, demonstrates the capabilities of this new CAR T Organ-Chip workflow. After watching, you will learn how to use Organ-Chips to model CAR T-cell therapy administration, vascular attachment, migration, and antigen-specific killing—all in a single model. Additionally, Luke Dimasi, Sr. Director of Product Management, provides an overview of Emulate Organ-on-a-Chip technology and how it can be used to faithfully model the complexities of human biology across a variety of applications. 

In this webinar, you will learn about: 

• Emulate Organ-on-a-Chip technology and its applications in disease research and drug development. 
• Modeling CAR T-cell recruitment and solid tumor cell killing in a unified Organ-Chip assay. 
• Evaluating co-therapeutics to enhance CAR T recruitment and killing efficiency.  
• Conducting comprehensive CAR T efficacy analysis through techniques such as confocal imaging with automated quantification, effluent analysis of cytokine release, and immune cell extraction and phenotyping. 

Metastasis in breast cancer is a leading cause of mortality. In particular, breast cancer that metastasizes to the bone significantly worsens patient outcomes; however, the mechanisms underlying this process remain poorly understood. While previous studies have focused on how interactions between cancer cells and bone marrow contribute to cancer metastasis, significantly fewer studies have been completed that aim to understand how osteocytes—the primary regulators of the bone environment—influence metastatic breast cancer progression.

This case study summarizes how Dr. Stefaan Verbruggen and colleagues at Queen Mary University of London used Emulate Organ-Chips with the Human Emulation System to create a dynamic bone model of breast cancer metastasis, enabling them to elucidate the molecular mechanisms governing the interplay between cancer cells and osteocytes under conditions of mechanical loading.

In this case study, you will learn how:

• Researchers used Organ-Chips to recapitulate breast cancer metastasis to the bone.
• Mechanical stimulation plays a key role in early- and late-stage breast cancer metastasis.
• Organ-Chips can benefit cancer researchers through enabling tissue co-cultures and the selective application of shear stress in a complex 3D tumor microenvironment.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy holds great promise for treating solid tumors. However, there are significant challenges in developing an effective CAR T cell solid tumor therapy due to a lack of human-relevant models that adequately capture mechanisms of CAR T cell recruitment—a critical rate-limiting step in CAR T cell efficacy that is often overlooked.

View this poster, presented at IMMUNOLOGY2024, to learn how Emulate researchers developed a novel system for investigating both the recruitment and killing capacity of CAR T cells in an Organ-Chip model.

Click here to watch Emulate Principal Scientist Anita Mehta’s full poster walkthrough from IMMUNOLOGY2024.

Chimeric antigen receptor (CAR) T-cell therapy shows significant potential in treating various human cancers. Unfortunately, researchers have faced difficulty in adapting this therapy to target solid tumors, where CAR T cells face unique challenges, such as antigen heterogeneity, an immuno-suppressive microenvironment, and T-cell exhaustion.  

However, none of these challenges matter unless the CAR T cells can extravasate out of the blood stream and successfully migrate to the site of the tumor—an often-overlooked yet critical rate-limiting part of the process that cannot be modeled in conventional cell cultures. 

This application note explains how Organ-Chips can be used to model the entire journey of solid tumor CAR T-cell therapy in a vascularized cancer cell line model. 

In this application note, you will learn how Organ-Chips can be used to: 

• Evaluate CAR T-cell vascular recruitment and killing efficacy in a single, unified assay. 
• Assess antigen-specific killing and degranulation through a range of imaging and effluent-based analysis. 
• Investigate co-therapeutic efficacy, as shown by proof-of-concept IL-2 data. 
• Adapt the workflow to study a diverse range of solid tumor cell lines, immunotherapies, and co-therapeutics. 

In this webinar from Drug Discovery Day 2024, Carly Strelez, PhD, discusses her work using Organ-on-a-Chip technology to better understand colorectal cancer progression and transform approaches to personalized medicine.

Speaker:

Chimeric antigen receptor (CAR) T-cell therapy holds great promise as a treatment for a variety of human cancers, but successfully adapting this treatment for solid tumors has remained elusive. A major challenge is that conventional 2D cell models are unable to recreate the journey that solid tumor CAR T-cell therapy undergoes in the human body. In this video, see how Emulate Organ-Chips can be used to evaluate the efficacy of CAR T-cell therapies and provide a more comprehensive model that integrates both the recruitment and killing aspects of CAR T function.

Want to learn more?

Explore our solutions for Cell Therapy

Read the CAR T application note

Watch our on-demand webinar: Evaluating CAR T-Cell Therapy Recruitment & Efficacy with Organ-on-a-Chip Technology

Lena Schorr is a PhD student in the Epithelium Microenvironment Interaction Laboratory (EMIL) led by Dr. Jens Puschhof in the Microbiome & Cancer Division of the German Cancer Research Center in Heidelberg. She is investigating microbe-host interactions using organoid and organ-on-chip models to further elucidate the role of intracellular bacteria in colorectal cancer progression and metastasis.  

Fusobacterium nucleatum, a prominent bacterium that is enriched in colorectal cancer, is her target bacterium of interest. She studied biology and immunology at the FAU in Erlangen, Germany, did research stays at the Rockefeller University and Roche and is now in the DKFZ International PhD Program. She has been awarded several stipends such as the DAAD scholarship and was a participant and team leader in iGEM, the world’s largest synthetic biology competition. 

This presentation is from a featured session at Netherlands MPS Day, which took place on 11/15/2023.

Webinar Abstract

Featured session at Boston MPS Day, which took place on 11/1/2023.

Webinar Abstract

Chimeric antigen receptor (CAR) T-cell therapy holds great promise as a treatment for a variety of human cancers. While there are 5 FDA-approved CAR T therapies for liquid tumors, successfully adapting this treatment for solid tumors remains elusive. 

A major reason why solid tumors are so much harder to treat with CAR Ts is because of their vastly different microenvironment. To effectively kill solid tumor cells, CAR Ts must first exit the vasculature at the tumor location, infiltrate deeply into the tumor, lock in with tumor-specific antigens, and finally, kill the cancer cells. 

It’s a long, complicated journey, and one that conventional models cannot capture due to their simplicity. Enter Organ-Chips. 

Emulate Organ-Chips can help address these challenges by enabling human-relevant and more comprehensive recapitulation of immunotherapy efficacy. In this webinar, Chris Carman, PhD, shared data from proof-of-concept studies showing how Organ-Chips can be used to evaluate the efficacy of CAR T-cell therapies and provide a system that integrates both the recruitment and killing aspects of CAR T function.

In this webinar, you will learn how Organ-Chips can be used to:

• Assessing CAR T recruitment and killing in a novel, adaptable Organ-Chip workflow. 
• Evaluating co-therapeutics to enhance CAR T recruitment and efficacy. 
• Creating a co-culture lung cancer model with A549 carcinoma cell line and lung-specific microvasculature. 
• Evaluating CAR T efficacy through multi-modal analysis, including confocal imaging and quantification, cytokine release, and effluent analysis.