New CAR T-cell therapy study indicates promise in solid malignancies.

Researchers at Peter Mac have created a fresh method for treating solid cancer tumors with chimeric antigen receptor (CAR) T-cell therapy.

Using T-cells that are present in the body naturally and are a vital component of the immune system, CAR T-cell therapy is a cutting-edge type of immunotherapy that uses these cells to target and kill infected cells. As a one-time procedure, these T-cells are gathered, modified with the CAR receptor, and then reinfused to combat the cancer cells.

In contrast to traditional T-cells, the most recent study, led by Peter Mac and published this week in Science Translational Medicine, uses younger, stem-like T-cells. The discovery that these cells, also known as T-stem-like CAR T-cells, have a higher capacity for reproduction when carrying the CAR receptor is exciting.

“While CAR T-cell therapy has been approved for certain types of blood cancers such as leukemia, lymphoma, and myeloma, its success in solid cancers is limited.” This is because to variables such as inadequate CAR T-cell growth, persistence, and weariness in the battle against the tumor.”

Professor Paul Neeson, 

This study is a significant step toward CAR T-cell therapy being effective in solid cancers, according to Professor Paul Neeson, head of the Peter Mac Human Immunology Translational Lab.

Credit: Peter MacCallum Cancer Center

“While CAR T-cell therapy has been approved for the treatment of some blood cancers, including leukemia, lymphoma, and myeloma, its effectiveness in treating solid cancers is limited.” Poor CAR T-cell expansion, perseverance, and exhaustion from fighting the tumor are some of the causes of this, he added.

Importantly, these T-stem-like CAR T-cells have enhanced anti-tumor activity in four pre-clinical models as well as in culture dishes. In fact, they completely eliminated pre-existing solid tumors when combined with the immune checkpoint medication anti-PD1.

“In addition, they endure over time, showing that they possess all the characteristics of CAR T-cells, which have demonstrated outstanding success in treating blood cancers.”.

First, the study developed a production protocol that produces fully functional stem-like CAR T-cells in a condensed six-day time frame as opposed to the usual 14 days, paving the way for a future process that is more efficient and scalable.

These important results support the use of production techniques to create stem-like CAR T cells for clinical applications.

“Our goal is to treat two pediatric leukemias that are unresponsive to therapy with these cells. We are confident that our protocol will enable the CAR-T cell product to have stable anti-tumor activity and the critical capacity for persistence,” Prof. Neeson said.

“Once we demonstrate the safety of these cells, we will focus on developing this therapy for pediatric solid cancers like osteosarcoma and neuroblastoma.”.

More information: Deborah Meyran et al, T STEM -like CAR-T cells exhibit improved persistence and tumor control compared with conventional CAR-T cells in preclinical models, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abk1900

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