Promise and Potential: Cell Therapies for Pediatric Patients

Interview with Professor Dr. Peter Bader

Head of the Division for Stem Cell Transplantation and Immunology
Department for Children and Adolescents, University Hospital Frankfurt, Goethe University

The development and use of cell and gene therapies are rapidly expanding across the globe, offering powerful treatments to help address challenging diseases like childhood leukemia and spinal muscular atrophy (SMA). In this interview with Prof. Dr. med. Peter Bader, Head of the Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine in the Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, we learn about both the potential of these therapies as well as the clinical challenges associated with such personalized forms of medicine.

Cell and gene therapies are seen as the medicine of the future. What do you view as some of the greatest promises or patient outcomes for these therapies?

The first cell therapy was stem cell transplantation. Today, we have cell therapies that work specifically against leukemia cells—this is an important difference from where we started two to three decades ago. The therapeutic cells given are genetically engineered to unerringly eliminate these malignant cells.

In contrast to cell therapy where cells are transferred to the patient, gene therapy involves transfer of genetic material into appropriate cells of the patient in order to achieve gene correction. This is a wide field that is still being defined, but there are gene therapies that are already in clinical use. These target disorders are related to the blood and the immune system, such as congenital anemia syndrome, thalassemia, adrenoleukodystrophy, metabolic disorders and so forth. In these, the correction of hematopoietic stem cells takes place by excision of genes or exchange of genes. After 30 years of intensive research, we’ve had clinical successes in these areas over the past 10 years.

What significance do cell and gene therapies already have in practice in the patients you serve?

Cell therapy is starting to gain importance as a treatment for children, adolescents and young adults with acute leukemias and anemia syndromes. These therapies offer hope to patients with recurrent leukemia, where conventional treatment is not successful. Administering and treating patients with these cell therapeutics is actually easier than performing a transplant, but we need long-term evidence to show that the therapies have the same effectiveness as a transplant.

Your center is included in a study group that is researching CAR-T, currently one of the best-known cell therapies. Can you tell us how CAR-T treatment is applied in practice?

In Germany, we were the only center that had the privilege to participate in the multicenter phase II study (note: CCTL019B2202 study) . Enrolled were pediatric patients with B-cell acute lymphoblastic leukemia of the B precursors, children and adolescents up to the age of 25 who either relapsed for the second time, relapsed after transplantation or did not respond to therapy at all.

CAR-T-cell therapy is a complex cell therapy procedure. First the patient's own white blood cells are removed by leukapheresis in an adequate number and T cells are isolated therefrom in the laboratory. These are genetically modified using an inactive viral vector to express a so-called chimeric antigen receptor (CAR) on their cell surface, which targets the antigen CD19. After binding of these CAR-T cells to the CD19-bearing leukemic target cells, an immune response is activated and triggered resulting in destruction of the cancer cells.

During the manufacturing period of the patient’s CAR-T-cells (about 6 weeks) a bridging therapy might be required to maintain disease control and prevent progression. Before receipt of the laboratory-produced and augmented CAR-T cells, the patient receives a lymphodepletion chemotherapy in order to ensure good starting conditions for CAR-T cell expansion in the body.

In the acute phase of about 1-2 weeks after CAR-T-cell administration complications like cytokine-release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) may occur. These can be severe, which is why treatment should be done in experienced centers.

Of course a careful long-term follow-up is necessary for patients receiving CAR-T-cell therapy.

Research seems to indicate that about 90% of patients respond to CAR-T therapy. Is that correct?

Yes, these are the numbers for a response to therapy. This can be compared to the figures from the frontline treatment of a patient with cortisone, with 90-95% of patients responding to the therapy and after another two weeks, all are in remission. But the question is, does that last? A 90% response after 28 days is sensational for this high-risk group, but retention of the remission lasting two to three years is the real goal.

You can access the entire interview of our discussion, where Dr. Bader talks in depth about other key issues facing cell therapy development, including:

  • The clinical challenges and developments associated with providing these therapies to patients, including the complexities of creating therapies using a patient’s own cells
  • Success rates using these therapies with pediatric leukemia patients
  • The challenges of scaling the production of cell therapies and addressing their costs
  • The future potential of these therapies

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