New findings in T-cell research may lead to improved treatment of solid tumors

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Singapore – A field study led by the Agency for Science, Technology and Research (A*STAR) shows that blocking the function of two proteins, G9a and GLP, during the cell therapy manufacturing process can make immune cells more effective in fighting cancer. I discovered that it can be done.These findings published in the journal Nature Communications, It can accelerate the development of innovative therapies that benefit cancer patients and move us closer to more effective targeted therapies for solid tumor cancers.

Solid tumors are the leading cause of cancer-related death worldwide1. Traditional treatments such as chemotherapy, radiation therapy, and surgery are available, but their effects on solid tumors, especially advanced-stage cancers, vary.2. Although T-cell therapy has been highly successful in targeting liquid tumors such as hematological cancers, similar effects have not been observed in solid tumors such as breast, liver and brain tumors.

Engineered T cells are usually introduced into the patient’s bloodstream as part of the treatment. They are in the same environment as liquid tumours, making them easier to spot and target. However, for solid tumors, modified T cells are physically challenged, such as moving through dense tissue structures in the body and encountering other cells and molecules that can adversely affect their function. face physical and molecular obstacles.3.

Researchers and clinicians from A*STAR’s Institute of Molecular and Cellular Biology (IMCB) and Singapore Immunology Network (SIgN) and Duke NUS Medical School collaborate to improve the efficiency of cognition and immune cells, T cells We sought innovative approaches to Removes cancer cells.

The research team, led by Dr. Andrea Pavesi, IMCB Senior Fellow at A*STAR, will provide a comprehensive analysis of epigenetic agents that may influence the efficacy of genetically engineered T cells to enhance anti-tumor activity. It was conducted. The research team used 2D and novel 3D assays that mimic the physical environment encountered by T cells to locate and target cancer cells within the human body. Drugs targeting the G9a and GLP proteins were administered to immune cells during the cell expansion process of cell therapy performed in the laboratory. The drug was then washed out before the engineered immune cells were reintroduced into the patient’s body, thus eliminating side effects from the drug. The results of the study showed that the drug helped increase the anti-tumor function of genetically engineered immune cells, increasing the production of granzymes, proteins that help locate and eliminate target tumor cells. showed.

Leveraging the immune cell profiling capabilities of Dr. Giulia Adriani, Principal Investigator of A*STAR’s SIgN, and patient samples from Duke-NUS, the findings were validated using established cell lines and patient-derived immune cells. , was validated. Effect of blocking her G9a and GLP activity in improving the efficiency of T cell therapy. The results showed that the drug enhanced the anti-tumor function of genetically engineered immune cells.

This means better patient outcomes, including improved survival and quality of life. It also has broad implications for all cell therapies targeting solid tumors. Patients with weakened immune systems who normally require immune cells from healthy donors for cell therapy treatment may also benefit from treatment with their own immune cells. This reduces the possibility of the patient’s body rejecting the cells and the effects of using incompatible cells. This drug, which is used to block G9a and GLP activity, has great potential for further development, making it an attractive therapeutic option in cancer treatment.

Dr. Andrea Pavesi, senior fellow at IMCB at A*STAR and lead author of the study, said, “The approach of improving the individual anti-tumor activity of each immune cell addresses many of the limitations of T-cell therapy. and can improve treatment efficacy.” Our findings will advance the development of effective treatments for solid tumor cancers and help improve lives. “

Antonio Bertoletti, Professor of Emerging Infectious Diseases Program at Duke University, said: Fight diseases such as cancer. This finding could help improve cell therapy using both patient-derived and donor-derived immune cells, potentially benefiting a range of patients. We are working towards a successful clinical trial and hope to bring this method to market to improve patient outcomes. “

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1 International Cancer Research Fund

2 The Emerging State of Immune Cell Therapy, Cell, Vol. 181, No. 1, April 2020

3 Adoptive Cell Therapy in Solid Tumor Malignancies: A Review of the Literature and Future Challenges, Journal for ImmunoTherapy of Cancer, Vol. 9, No. 7, July 2021

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