Studying TCR T cell anti-tumor activity in a microfluidic intrahepatic tumor model

Giulia Adriani1, Andrea Pavesi2, Roger D Kamm3

  • 1BioSystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.

Insights

This study presents a novel microfluidic model for rapid preclinical testing of adoptive cell therapy (ACT) in liver cancer. The model assesses T cell activity within the tumor microenvironment to optimize immunotherapies.

Area of Science:

  • Immunology
  • Oncology
  • Biomedical Engineering

Background:

  • Adoptive cell therapy (ACT) shows promise for cancer treatment but faces challenges due to the tumor microenvironment.
  • Understanding the tumor microenvironment is crucial for improving ACT efficacy and overcoming treatment barriers.

Purpose of the Study:

  • To develop a rapid and reproducible preclinical model for evaluating ACT strategies.
  • To investigate the role of monocytes and the liver tumor microenvironment in ACT efficacy.
  • To optimize T cell-based immunotherapies through advanced preclinical testing.

Main Methods:

  • Development of a 3D intrahepatic tumor model utilizing microfluidic technology.
  • Screening of T cell-based immunotherapeutic strategies within the microfluidic system.
  • Assessment of factors like cytokine administration and oxygen levels mimicking the liver tumor microenvironment.

Main Results:

  • The microfluidic system enables quantitative assessment of T cell anti-tumor activity.
  • The model effectively simulates key aspects of the liver tumor microenvironment.
  • The platform facilitates the evaluation of therapeutic strategies under various conditions.

Conclusions:

  • The developed 3D microfluidic assay is a valuable tool for preclinical screening of ACT.
  • This model aids in optimizing existing immunotherapies and designing novel treatment strategies.
  • It provides a faster and more reproducible method for evaluating ACT potential in patient therapy.

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.0K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.0K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.4K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.8K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.1K