Why do cancers go into remission for a long time after CAR-T cell therapy?

News

Why do cancers go into remission for a long time after CAR-T cell therapy?

Researchers from UCL, Great Ormond Street Hospital, and the Wellcome Sanger Institute have revealed findings explaining why some children experience extended periods of remission after receiving advanced CAR-T cell therapy for leukemia.

Why do cancers go into remission for a long time after CAR-T cell therapy?

In their study, the research team identified a genetic feature within CAR T cells used to treat childhood leukemia, which indicates long-lasting efficacy. This breakthrough offers hope for optimizing treatment methods, identifying patients who respond best, and enhancing long-term remission outcomes.

Published recently in the journal “Nature Medicine,” this collaborative research merged cutting-edge immunotherapy design knowledge with state-of-the-art computational analysis techniques to pinpoint the genetic features of CAR-T cells that are most effective over the long term.

In recent years, CAR-T cells, genetically engineered T cells designed to target leukemia, have become the established treatment for children with rare leukemia (B-cell acute lymphoblastic leukemia or B ALL) that has relapsed or is unresponsive to conventional therapies.

One of the key factors in determining whether the treatment leads to long-term remission, effectively preventing cancer from returning in children, is the survival time of CAR-T cells within the body. Up to this point, little was known about the longevity of these cells within the body, raising questions about whether this therapy could have a sustained effect without further intervention.

As part of the CARPALL study, a collaborative research group from Great Ormond Street Hospital (GOSH), the Wellcome Sanger Institute, and UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) worked alongside families of patients who had received CAR-T cell therapy (referred to as AUTO1) for several years, seeking to understand why some CAR-T cells persist in the body for an extended duration.

This work lays the foundation for understanding why some CAR-T cells persist long-term. The research team’s aim is to build upon the characteristics discovered in this project, identifying key markers within the cell population and ultimately determining whether it’s possible to detect or even create CAR-T cells that can endure long-term before treatment begins.

Dr. Nathaniel Anderson, the first author of the paper and a researcher at the Wellcome Sanger Institute, stated, “Through cutting-edge single-cell genomics research, we have, for the first time, deciphered the enduring code of pediatric CAR-T cells very clearly. We hope our study provides the first clues about why some CAR-T cells persist for extended periods — knowledge that is crucial for keeping children cancer-free after treatment. Ultimately, this work will help us further refine this life-changing therapy.”

Dr. Sara Ghorashian, co-first author, pediatric hematologist at GOSH, and honorary senior clinical lecturer at UCL GOS ICH, remarked, “This data provides the first glimpse into the characteristics of long-lasting CAR-T cells, which not only cure ALL in the children we studied but also in adults with different types of leukemia using different CAR-T cell products. Consequently, this leads us to believe that this feature might reveal the mechanisms of CAR-T cell persistence more broadly and enable us to develop better treatment methods. We are indebted to the children and families who made studies like ours possible – only through their dedication can we build an understanding of these new therapies and offer improved treatment for children worldwide.”

Delving Deep into CAR-T Cells

A research team has delved into the cells of ten children who participated in a groundbreaking clinical trial called the CARPALL trial. These children, who had received initial CAR-T cell therapy, continued their treatment for up to five years.

This research has shed new light on why some CAR-T cells persist in patients’ blood while others vanish prematurely, a phenomenon that in certain cases can lead to cancer relapse.

Scientists employed single-cell analysis techniques at the genetic level to understand the workings of these long-lasting CAR-T cells. They identified a unique “trait” in these long-lasting CAR-T cells in the blood.

This trait suggests that these long-lasting CAR-T cells undergo a transformation into a different state, enabling them to continue eradicating cancer cells within the patient’s body.

Crucially, this trait was observed not only in different cells and patients but also in adults treated with different CAR-T cell products for various types of leukemia. It was notably absent in other types of immune cells.

This indicates that the identified trait might not just be a marker for these long-lasting cells but could be the very reason they persist within the body, providing children with longer-lasting relief from their illnesses.

As part of the study, researchers identified key genes within CAR-T cells that appear to contribute to their long-term presence in the body. Importantly, these genes will serve as a starting point for future research to determine enduring markers in CAR-T cell products’ manufacturing processes, ultimately enhancing their effectiveness.

Dr. Sam Behjati, a co-first author of the study, group leader, Wellcome Sanger Institute Wellcome Senior Research Fellow, and Honorary Consultant in Pediatric Oncology at Addenbrooke’s Hospital, Cambridge, said, “This research represents an exciting step forward in our understanding of CAR-T cell persistence, illustrating the power of collaborative science and the integration of cutting-edge genomics with pioneering clinical research. We must continue to develop and refine these new therapies to help more children with leukemia worldwide.”

The Dedication of Research Families

Such research wouldn’t have been possible without the dedication of the children and families who participated. In order for scientists to study the long-term survival of these cells, children had to continue donating cells for research within five years of their initial treatment.

Austin was diagnosed with B ALL at the age of two and had experienced three relapses and extensive treatments, including two bone marrow transplants, by the age of eight. By his fourth relapse, he had exhausted all conventional treatment options. In October 2016, as part of the CARPALL clinical trial, Austin received CAR-T cell infusion.

More than six years later, at the age of 14, Austin remains cancer-free, with long-lasting CAR-T cells still detectable in his blood. He is one of the ten children who have been continuously contributing samples to this research since their infusions.

His father, Scott, said, “It’s no exaggeration to say that without this research, Austin wouldn’t be alive. The research team at GOSH has given us so much, and we want to give back. Being part of this research not only gave us that opportunity, but we hope Austin’s data will help other families like ours in the future. In fact, we love coming back to GOSH to see our team; they’ve become a part of our lives. I’m incredibly proud that Austin has been able to be part of this journey.”

The ongoing commitment to research helps researchers gain a better understanding of cutting-edge therapies and improve these treatments for future families.

Dr. Henry Stennett, Research Information Manager at Cancer Research UK, said, “We know that immune therapies like CAR-T cell therapy have seen tremendous success over the years, but they don’t work for all patients, and we need to keep working to understand why. Research like this is crucial in getting us closer to making immune therapies more effective for more cancer patients.”

(source:internet, reference only)

Disclaimer of medicaltrend.org

Important Note: The information provided is for informational purposes only and should not be considered as medical advice.