Leading expert in pediatric leukemia and precision medicine, Dr. Shai Izraeli, MD, explains how novel cancer immunotherapies are revolutionizing treatment for relapsed and treatment-resistant childhood acute lymphoblastic leukemia (ALL). He details three effective types of immunotherapy—antibody-drug conjugates, bi-specific T-cell engagers, and CAR T-cell therapy—that are moving from clinical trials into frontline use, offering new hope for curing the most challenging cases.
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Advanced Immunotherapy Options for Relapsed Pediatric Leukemia
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- The Immunotherapy Revolution in Pediatric ALL
- Learning from Immunology: The B-Cell Paradigm
- Antibody-Drug Conjugates: The Trojan Horse
- Bi-Specific Antibodies: Engaging the Immune System
- CAR T-Cell Therapy: Engineering a Cure
- The Future of Pediatric Leukemia Treatment
The Immunotherapy Revolution in Pediatric ALL
Dr. Shai Izraeli, MD, describes an incredibly exciting time in the treatment of relapsed pediatric acute lymphoblastic leukemia. This excitement stems directly from the rapid development of effective cancer immunotherapy. These groundbreaking treatments are currently available for B-cell acute lymphoblastic leukemia, which constitutes approximately 85% of all pediatric ALL cases. Dr. Anton Titov, MD, highlights that these advances are transforming outcomes for children with the most difficult-to-treat forms of leukemia.
Learning from Immunology: The B-Cell Paradigm
The foundation for modern immunotherapy was laid by understanding a hereditary condition called Bruton agammaglobulinemia. Dr. Shai Izraeli, MD, explains that patients with this disease have no B cells, a condition that was once lethal. The development of immunoglobulin replacement therapy proved that patients could survive and thrive without B cells. This critical insight opened the door for therapies designed to target surface antigens on immune cells, knowing that the resulting loss of normal B cells could be medically managed.
Antibody-Drug Conjugates: The Trojan Horse
One powerful type of cancer immunotherapy is the antibody-drug conjugate. Dr. Shai Izraeli, MD, uses the analogy of a Trojan horse to describe how these medications work. An antibody, such as inotuzumab (Besponsa), is designed to recognize and bind to leukemic cells. The cancer cell internalizes the antibody, unaware that it is carrying a potent toxin. Once inside, the toxin is released, effectively killing the cancer cell from within and providing a targeted mechanism for treating relapsed leukemia.
Bi-Specific Antibodies: Engaging the Immune System
Another innovative approach involves bi-specific T-cell engager antibodies. Dr. Shai Izraeli, MD, describes these as antibodies with two heads. One head targets an antigen on the leukemia cell, while the other head binds to a T cell—a key soldier of the patient’s own immune system. A prime example is the medication blinatumomab (Blincyto). This antibody physically brings the patient’s T cells into direct contact with the cancer cells, instructing the T cells to attack and destroy the leukemia, harnessing the body’s natural defenses against cancer.
CAR T-Cell Therapy: Engineering a Cure
Perhaps the most revolutionary development is chimeric antigen receptor (CAR) T-cell therapy. Dr. Shai Izraeli, MD, notes this achievement, pioneered by Israeli scientist Dr. Zelig Eshhar in the 1980s, is of Nobel Prize importance. In this treatment, a patient’s T cells are harvested and genetically engineered in a laboratory to express an antibody that targets B cells. These powerfully modified CAR T-cells are then infused back into the patient, where they seek out and relentlessly destroy leukemia cells, offering a potent and potentially curative option for relapsed disease.
The Future of Pediatric Leukemia Treatment
The impact of these immunotherapies is profound. Dr. Shai Izraeli, MD, emphasizes that these are not just treatments for relapsed leukemia; they are now being integrated into first-line therapy for children with high-risk disease. The conversation with Dr. Anton Titov, MD, underscores a major shift in pediatric oncology. The lessons learned from immunology and the success of engineered therapies like CAR T-cells are paving the way for a future where even the most resistant childhood leukemias can be successfully cured.
Full Transcript
Dr. Anton Titov, MD: Immunotherapy for relapsed pediatric leukemia treatment is now more common. Leading child leukemia and precision medicine expert discusses progress in child cancer treatment and lessons learned from immunology. Many children are now being cured of leukemia.
But unfortunately, in some children, leukemia returns. There is a relapse of leukemia. You specialize in therapy of treatment-resistant leukemia and relapsed leukemia.
What is new in treatment of relapsed leukemia?
Dr. Shai Izraeli, MD: In the field of acute lymphoblastic leukemia, we are in a very exciting time. The exciting time comes from the development of cancer immunotherapy. Currently cancer immunotherapy exists only for the most common subtype of acute lymphoblastic leukemia.
It is a B cell acute leukemia. It constitutes 85% of all acute lymphoblastic leukemia.
We learned a long time ago that it is a hereditary disease. It's called Bruton agammaglobulinemia. Patients with Bruton agammaglobulinemia have no B cells. It used to be lethal.
But now we have cancer medications that are called immunoglobulins. These are the antibodies. Children with Bruton agammaglobulinemia can grow and be adults after therapy with immunoglobulins.
We learned from Bruton agammaglobulinemia therapy that you can give immunoglobulins, antibodies. Then B cells are not essential for survival of patients. This really opened the door for treatment against surface antigens on the surface of the immune cells.
This is cancer immunotherapy that kills B cells. It kills both the normal and the leukemic cancer cells. But we can get over the loss of normal cells by giving immunoglobulins.
There are actually three types of cancer immunotherapy. All of them are now quite effective in the clinical trials. I believe they will enter therapy of relapsed leukemia.
Immunotherapy will be used in high risk leukemias as a first-line treatment.
Dr. Anton Titov, MD: One type of cancer immunotherapy are antibodies that are conjugated to toxins. The antibodies recognize the leukemic cells. Leukemia cells swallow the antibody.
But this antibody is like a trojan horse. Immunotherapy cancer medication also carries a toxin. This toxin is released inside the leukemia cells. Toxin kills cancer cells.
That's one example. The name of medication is inotuzumab. It is an example of leukemia treatment with cancer immunotherapy antibody.
There are other type of leukemia treatment antibodies. These are called bi-specific antibodies. This is an antibody that has two heads.
One head targets the leukemia antigen. The other head targets T cell. This child leukemia therapeutic antibody brings T cells to the leukemic cells.
These are the patient's T cells. T cells are a type of immune cells. Antibody brings T cells to the vicinity of the leukemia cell. Then the T cell eats the leukemic cell.
An example of such leukemia cancer immunotherapy antibody is blinatumomab. This is an unbelievable development of genetic engineering.
T cells are called CAR T-cells. This leukemia therapy is very important. Maybe the Nobel Prize will be given for CAR T-cell therapy.
That this was invented by an Israeli scientist. His name is Dr. Zelig Eshhar. He developed them in the 1980s. He called them T-bodies.
In CAR T-cell therapy, immune T cells are harvested from the patient's body. Then in cell culture in the laboratory they are engineered. An antibody against B-cells is put into these T-cells.
Then these T-cells are injected back to a patient. Then these T-cells are coming and finding the leukemia cells, and they kill cancer cells.
Dr. Shai Izraeli, MD: These are the incredibly exciting new cancer treatments that we have now against relapsed child leukemia.