USC scientists achieve continuous production of cancer-resistant immune cells

🧬 Brief scientific summary

A team of scientists at the University of Southern California (USC) has succeeded in developing an innovative method for producing immune cells that are renewable and expandable without limits in the laboratory. The focus was on granulocyte-monocyte progenitors (GMPs), which are the precursor cells to macrophages, cells that play a crucial role in fighting cancer. The discovery makes it possible to genetically engineer these cells to improve the immune response against cancer cells, opening new horizons for treating solid tumors and some other related diseases.

🧪 Innovation in culturing immune system cells

GMPs are precursor cells that give rise to macrophages and other types of immune cells. These cells form an important line of defense against infection and have properties that can be leveraged to fight cancer. Immunology research has often focused on hematopoietic stem cells, which have long-term self-renewal capacity, but this study revealed that GMPs may also possess that ability when the proper conditions are provided.

These cells can also be expanded and kept active for a long time in the laboratory, while preserving their functional characteristics, forming a solid basis for producing large numbers of powerful immune cells.

🧠 The self-renewal capacity of GMPs

Until now, it had not been thought that GMPs possessed self-renewal ability, a feature that allows cells to divide repeatedly without losing their identity or core functions, which is usually considered the preserve of stem cells alone.

But this study showed that under the influence of a specific chemical mixture that keeps the cells in a stage before full maturation, GMPs can keep dividing continuously while retaining their ability to generate macrophages and other effective immune cells.

This property is very important because it provides the possibility of continuous, unlimited production of specialized immune cells for fighting disease, especially cancer.

🩺 The importance of macrophages in cancer treatment

Macrophages are the first immune system cells to arrive at infected sites or tumors. They are distinguished by their innate ability to engulf and kill cancer cells and regulate the surrounding immune response.

Despite the great success of T-cell therapies in blood diseases, macrophages are a good candidate for treating solid tumors, which pose a major challenge for conventional treatments.

However, there are challenges in using mature macrophages directly, such as:

• Difficulty multiplying them in large quantities outside the body.
• Challenges in genetically modifying them.
• Loss of effectiveness after freezing and storage.
• Their concentration in certain organs such as the lungs and liver, which reduces their effective distribution.

🌱 Focusing on precursor GMPs to macrophages

To overcome these difficulties, the researchers focused on GMPs, which are more fully matured and therefore technically easier to work with than mature macrophages.

Using a carefully selected chemical mixture, the team managed to prevent GMPs from turning into other types of immune cells and keep them for many months in the laboratory with the ability to expand their numbers, while ensuring their capacity to later produce functional macrophages.

This achievement was independently confirmed in another laboratory at Stanford University, which strengthens the credibility of the method.

🔬 Genetic engineering of GMPs against cancer

The next step in the study was to genetically modify GMPs to develop immunity directed against cancer.

The researchers introduced cloned receptors known as Chimeric Antigen Receptors (CARs), which enable the cells to recognize specific markers on the surface of cancer cells.

In addition, stimulatory signals were added to activate neighboring immune cells that enhance the T-cell response against the tumor.

The standout advantage is that these signals remain effective even in the absence of immune matching between donor and patient, opening the door to using these cells as ready-made off-the-shelf therapies to save time and effort in treating patients individually.

When these cells were tested on mice, they settled in the bone marrow and hematopoietic tissues, and continued producing the modified immune cells that showed the ability to delay the growth of solid and blood tumors.

The performance of cells containing CAR receptors and activation signals was much stronger compared with cells modified with only one component.

🧬 Treatment prospects and future applications

The impact of this technique was not limited to cancer alone; experiments on an animal model with a chronic inherited inflammatory disease known as chronic granulomatous disease showed that treatment with GMP cells helped the mice regain their ability to resist bacterial infection.

This supports the idea that the use of GMPs is not limited to cancer therapies alone, but could extend to other immunodeficiency diseases as well.

The researchers concluded that choosing the appropriate developmental stage of cells is important when developing immunotherapies, rather than focusing only on improving CAR receptors themselves.

🧪 Key findings of the study

• The researchers were able to continuously expand GMPs in the laboratory for long periods.
• The preserved cells retained their functions and their ability to produce effective macrophages.
• Genetically modified GMP cells carrying CAR receptors were developed to enhance cancer-cell recognition.
• Molecular signals were added to activate surrounding immune cells to strengthen the anti-tumor response.
• The technique proved successful in human and animal cells, and showed effectiveness in an animal model of cancer and immune diseases.

🧬 Conclusion

This discovery represents an important technical and scientific step toward producing powerful, renewable immune cells that can be adapted for a wide range of immunotherapies, especially for treating solid tumors and chronic immune diseases.

The strength of this technique lies in the ability to expand GMP cells and genetically modify them to produce directed and powerful immune responses, which could transform the future of immunotherapy toward the use of renewable immune cells in an effective and safe cancer-fighting way.

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