Cellular immunotherapy: do we hold the key to defeat cancer? Gregory Chodaczek’s new project

Grzegorz Chodaczek, PhD, leader of the Immunotherapy Research Group at Łukasiewicz – PORT, proves that properly selected gamma-delta T lymphocytes extracted from human blood can be an effective tool in the fight against the most dangerous brain tumor – glioblastoma multiforme. The nearly 15 million PLN that the Wroclaw scientists have just been awarded by the Medical Research Agency (ABM) will allow them to continue research aimed at developing a breakthrough anti-cancer therapy. Its base will be human immune cells.

Cellular immunotherapy: do we hold the key to defeat cancer? Gregory Chodaczek's new project

Glioblastoma multiforme is the most common malignant brain tumor with the worst prognosis and an average patient survival rate of about 10 months. What makes it so difficult to defeat? – Complete removal of the tumor by surgical methods, chemotherapy or radiation therapy is often not possible due to its location, and the tumor itself can further modify the activity of the patient’s immune system to its advantage, growing uncontrollably, Dr. Grzegorz Chodaczek explains.

The low effectiveness of current therapies forces the search for new treatment strategies, such as those using immune cells with natural anti-tumor activity and low sensitivity to the inhibitory effects of the tumor microenvironment. – One of the promising candidates is precisely the unique subtype of lymphocytes with expression of the gamma-delta T-cell receptor, which enables them to recognize and destroy disease-transformed cells under less restrictive conditions than the body’s numerically dominant alpha-beta T cells, the scientist explains, adding that the uniqueness of gamma-delta T cells lies in their ability to be harvested from healthy donors and to treat unrelated individuals with them. With other cell therapies for cancer (such as CAR-T cell therapy for leukemia), this has not been possible so far.

In pursuing a previous scientific project, Dr. Chodaczek compared the anti-tumor activity of different gamma-delta T-cell subtypes and observed that cells from some healthy donors performed much better against glioma cells than others, laying the groundwork for proposing new research.

In the “Optimization of blood donor selection for the production of therapeutic gamma-delta T lymphocytes for the treatment of malignant brain tumors” project just starting at Łukasiewicz – PORT, the Immunotherapy Research Group will analyze blood cells from a number of healthy individuals, which will be made possible through cooperation with the Prof. Tadeusz Dorobisz Regional Center for Blood Donation and Blood Donation in Wrocław.

The team emphasizes two things: – On the one hand, we want to study the cytotoxicity of gamma-delta T lymphocytes, i.e. their ability to kill cancer cells, and on the other hand, analyze what genetic factors and proteins, which are gene products, are responsible for the effectiveness of these cells in fighting cancer. Our goal is to find the “optimal donor” by identifying the characteristics of gamma-delta T cells that will most effectively fight glioma cells. Long-term, our research may contribute to the development of innovative anti-cancer therapies,” explains Dr. Chodaczek.

Funds obtained under the project will help equip the institute with further highly specialized devices (including a microscope for high-throughput analysis and a spectral flow cytometer) and expand equipment for spectrometric analysis of proteins, which will improve the acquisition and analysis of a huge amount of data. The remaining funds received from ABM will be used, among other things, to purchase reagents and consumables, genetic analysis (next-generation sequencing) and training, enhancing the team’s research competence. According to the leader of the Immunotherapy Research Group, who gained experience for many years at research units in the US, including the University of Texas MD Anderson Cancer Center in Houston and the La Jolla Institute for Immunology in San Diego: – Expansion of research equipment at Łukasiewicz – PORT thanks to government programs to support applied research allows us to operate at the level of the best scientific centers in the world. Investment in modern technologies is a step towards even greater efficiency and innovation of Polish science.

The goal of the next phase of research led by Dr. Grzegorz Chodaczek will be to develop technology to produce therapeutic cells for future clinical trials and to expand the use of gamma-delta T cells to fight other types of cancer.